Federal Practitioner

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.