BILATERAL CENTRAL RETINA VEIN OCCLUSION ASSOCIATED WITH OBESITY–HYPOVENTILATION SYNDROME (PICKWICKIAN SYNDROME) Mauricio Turati, MD,* Raul Velez-Montoya, MD,† Carmen Cecilia Gonzalez-Mijares, MD,† Adai Perez-Montesinos, MD,† Hugo Quiroz-Mercado, MD,† Gerardo Garcia-Aguirre, MD†
Purpose: To describe bilateral central retinal vein occlusion (CRVO) as a clinical manifestation of obesity– hypoventilation syndrome (pickwickian syndrome). Method: Case report. Patient: A 37-year-old Hispanic man with morbid obesity and obstructive sleep apnea who suddenly developed bilateral loss of vision. Results: Laboratory studies disclosed the following: hematocrit, 81%; body mass index, 55 kg/m2; PaCO2, 52 mmHg; and blood oxygen saturation (SaO2), 54%. Polysomnography demonstrated 45 obstructive apneas and 133 obstructive hypopneas, with abnormal movements of the inferior limbs during sleep. Discussion: Hypoxia and hypercapnia produce severe erythrocytosis that causes a change in blood viscosity. This may facilitate thrombus formation at the lamina cribrosa of both eyes manifested as bilateral CRVO. RETINAL CASES & BRIEF REPORTS 3:140 –143, 2009
From the *Glaucoma Department and the †Retina Department, Asociacio´n para Evitar la Ceguera en Me´xico, México City, México.
sometimes associated with hyperviscosity syndromes. In these syndromes, balance, described by Virchow in the 19th century, is disrupted, causing vein occlusion.4 We describe a man with morbid obesity and recent bilateral visual loss; diagnosis, treatment, and follow-up are discussed.
O
besity– hypoventilation syndrome was first described in modern literature by Burwell et al,1 who based part of their observations on one of Dickens’ characters. The syndrome is defined using the following criteria: obesity (body mass index, ⬎30 kg/m2); diurnal sleepiness; hypercapnia (PaCO2, ⬎45 mmHg); and obstructive sleep apnea (apnea– hypopnea index, ⬎30 per hour) or severe oxygen desaturation.2 Patients with obesity– hypoventilation syndrome may also present with morning headaches, fatigue, polycythemia, pulmonary hypertension, and right-sided congestive heart failure (cor pulmonale). If untreated, morbidity and mortality are considerably increased.3 Central retinal vein occlusion (CRVO) is a well-known disease that is
Case Report A 37-year-old Hispanic man presented to our hospital complaining of an 8-day history of progressive bilateral visual loss. He also had trouble staying awake during his job, small effort dyspnea, headaches, and very short sleep cycles (5 hours). His medical history was notable for high blood pressure, deep venous insufficiency, and ecchymosis in the lower limbs. He had morbid obesity (weight, 151 kg; body mass index, 55 kg/m2). Best-corrected visual acuity was 20/130 in the right eye and 20/100 in the left eye. Intraocular pressure was 14 mmHg in both eyes. Results of anterior biomicroscopic examination were unremarkable. Ocular movements, pupil responses, and lens examination results were normal for both eyes. Fundus examination of both eyes revealed clear vitreous, hyperemic optic disk with poorly defined edges, flame hemorrhages in the posterior pole, massive venous dilation and tortuosity, and mild macular edema. The right
Reprint requests: Raul Velez-Montoya, Vicente Garcı´a Torres Number 46, San Lucas Coyoacan, Mexico DF 04060; e-mail: [email protected]
140
141
BILATERAL CRVO IN OBESITY–HYPOVENTILATION SYNDROME
Fig. 1. Color fundus photographs of the right (A) and left (B) eyes show a hyperemic disk with poorly defined edges, flame hemorrhages, and severe venous dilation and tortuosity. There is also a subhyaloid hemorrhage in the right eye. C and D, Fluorescein angiography shows a delayed filling time, with earlyphase disk hyperfluorescence and no evidence of vascular leakage.
A
B
C
D
posterior pole also had a sub hyaloid hemorrhage. Neither eye had clinical evidence of retinal neovascularization. Fluorescein angiography showed early-phase disk hyperfluorescence, delay in vascular filling time, and hypofluorescence due to retinal hemorrhages. Vascular shunts or leakage due to neovascularization was not seen (Fig. 1). Complete blood cell count determination showed an erythrocyte count of 8.01⫻102 cells per liter, hemoglobin level of 23.9 g/dL, and hematocrit of 81.1%. Leukocyte count and blood chemistry levels were within normal limits. At this point, a diagnosis of bilateral CRVO and erythrocytosis was made. Treatment was started with oral acetylsalicylic acid (100 mg once a day) and captopril (25 mg twice a day) and prophylactic phlebotomy. At the same time, the patient began treatment at the sleep clinic of Instituto Nacional de Enfermedades Respiratorias (Mexico), where additional studies were performed (chest roentgenography, cranial computed tomography, blood gas analysis, electrocardiography, and polysomnography). Results of chest roentgenography and cranial computed tomography were normal. The electrocardiogram showed signs of right ventricle hypertrophy. Blood gas analysis showed hypercapnia (PaCO2, 52 mmHg) with hypoxemia (blood oxygen saturation [SaO2], 54%). Polysomnography demonstrated 45 obstructive apneas and 133 obstructive hypopneas (apnea duration, 20.4 seconds) and abnormal movements of the inferior limbs during sleep. With this new evidence, we made the following diagnoses: sleep apnea syndrome with severe hypoxemia, erythrocytosis, blood hyperviscosity, and obesity– hypoventilation syndrome (pickwickian syndrome). Treatment was restarted with a strict weight-loss diet, supplementary oxygen (1 L/min) via a nasal mask, and continuous positive airway pressure of 18 centimeters of water. Two years later, best-corrected visual acuity was 20/20 in the right eye and 20/25 in the left eye. Arterial blood pressure was 130/80 mmHg, weight was 81 kg (body mass index, 30.4 kg/m2), SaO2 was 98 mmHg, and PaCO2 was 37 mmHg. The erythrocyte
count was 5.30⫻1012 cells per liter, hemoglobin level was 16.6 g/dL, and hematocrit was 48.0%. The rest of the laboratory findings were within normal limits. Fundus examination showed a normal yellow disk with well-defined edges, resolution of retinal hemorrhages, and vessels with a normal appearance. Fluorescein angiography revealed a normal vascular filling time and hyperfluorescence in the inferior peripapillary area due to choroidal transmission secondary to alterations in the retinal pigment epithelium with no signs of vascular leakage (Fig. 2). All clinical changes, blood pressure, weight, and visual acuity were maintained at the last follow-up (February 2007).
Discussion Blood hyperviscosity syndrome is one of the less common causes of CRVO. It is characterized by an increase in blood components that slows transit through blood vessels, causing formation of thrombi. Waldenstro¨m macroglobulinemia is the most frequent hyperviscosity syndrome.5 There have been many reports of cases in which an increase of circulating immunoglobulins, secondary to multiple myeloma or by iatrogenic therapeutic administration, produced a state of sanguineous hyperviscosity causing bilateral CRVO.6,7 Pickwickian syndrome is a disease characterized by morbid obesity, hypercapnia, hypoxia, and obstructive sleep apnea.3 To our knowledge, the only reported ophthalmologic manifestations associated with this syndrome are disk edema, which can be associated with intracranial hypertension,8 and bi-
142
A
C
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 2
B Fig. 2. Color fundus photographs of the right (A) and left (B) eyes 2 years after the first visit show clearance of flame hemorrhages and no signs of neovascularization. C, Fluorescein angiography shows early-phase hyperfluorescence in the inferior peripapillary area due to choroidal transmission and some hypofluorescent spots surrounded by a hyperfluorescent halo, which are believed to be alterations in the pigment epithelium (the patient never received laser treatment). Filling time was normal, and there was no evidence of vascular leakage. D, Normal fluorescein angiogram.
D
lateral iris neovascularization. The exact cause of these manifestations is not known. Nevertheless, it has been suggested that hypoxia and hypercapnia can promote abnormal secretion of vascular endothelial growth factor via a nonischemic mechanism. The specific pathways are not known.9 In the present case, hypoxia and hypercapnia produced severe erythrocytosis (erythrocyte count, 8.01 m/mL; hemoglobin level, 23.9 g/dL; hematocrit, 81.1%), causing a change in blood viscosity (most likely causing formation of a thrombus in the lamina cribrosa of both eyes manifested by bilateral CRVO). Because of the patient’s age, we had to rule out other possible etiologies, especially blood hypercoagulable states. Serum levels of homocysteine, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies were all within normal limits or negative.4 The alterations detected by polysomnography together with the other laboratory findings confirmed the diagnosis of obesity– hypoventilation syndrome (pickwickian syndrome), which responds favorably to weight loss therapy and mechanical ventilation. Another disease that must be ruled out is pseudotumor cerebri. It presents most frequently in obese women in their mid-20s to 30s. Common presenting signs are diplopia, cranial nerve palsies, nausea, vomiting, dizziness, neck stiffness, tinnitus, inferior limb paresthesias, and arthralgias. There is high opening
pressure when lumbar puncture is performed, with normal cerebrospinal fluid. We did not perform lumbar puncture in our case because all clinical and laboratory findings pointed to a retinal vascular condition rather than cranial hypertension.10 In the current case, clinical improvement of the fundus with supplemental oxygen administration with continuous positive airway pressure is notable. This case demonstrates that respiratory therapy with continuous positive airway pressure can be useful in the treatment of bilateral CRVO associated with obesity– hypoventilation syndrome. Key words: obesity– hypoventilation syndrome, pickwickian syndrome, central retinal vein occlusion, hyperviscosity, polycythemia. References 1.
2.
3. 4.
5.
Burwell CS, Robin ED, Whaley RD, Bickelmann AG. Extreme obesity associated with alveolar hypoventilation—a pickwickian syndrome. 1956. Obes Res 1994;2:390–397. Akashiba T, Akahosi T, Kawahara S, et al. Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study. Intern Med 2006;45:1121–1125. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005;118:948–956. Lahey JM, Tunc¸ M, Kearney J, et al. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology 2002;109:126–131. Menke MN, Feke GT, McMeel JW, et al. Hyperviscosity-
BILATERAL CRVO IN OBESITY–HYPOVENTILATION SYNDROME
6.
7.
related retinopathy in Waldenstro¨m macroglobulinemia. Arch Ophthalmol 2006;124:1601–1606. Hayasaka S, Ugomori S, Kodama T, et al. Central retinal vein occlusion in two patients with immunoglobulin G multiple myeloma associated with blood hyperviscosity. Ann Ophthalmol 1993;25:191–194. Oh KT, Boldt HC, Danis RP. Iatrogenic central retinal vein occlusion and hyperviscosity associated with high-dose intravenous immunoglobulin administration. Am J Ophthalmol 1997;124:416–418.
8. 9.
10.
143
Wolin MJ, Brannon WL. Disk edema in an overweight woman. Surv Ophthalmol 1995;39:307–314. Duh EJ, Finkelstein D, Schneider T, et al. Bilateral iris neovascularization as the initial sign of obesity-hypoventilation (pickwickian) syndrome: hypoxia/hypercapnia as a stimulus for angiogenesis. Arch Ophthalmol 2000;118: 1298–1300. Chern S, Magargal LE, Brav SS. Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Ann Ophthalmol 1991;23:54–57.
Purpose: To describe bilateral central retinal vein occlusion (CRVO) as a clinical manifestation of obesity– hypoventilation syndrome (pickwickian syndrome). Method: Case report. Patient: A 37-year-old Hispanic man with morbid obesity and obstructive sleep apnea who suddenly developed bilateral loss of vision. Results: Laboratory studies disclosed the following: hematocrit, 81%; body mass index, 55 kg/m2; PaCO2, 52 mmHg; and blood oxygen saturation (SaO2), 54%. Polysomnography demonstrated 45 obstructive apneas and 133 obstructive hypopneas, with abnormal movements of the inferior limbs during sleep. Discussion: Hypoxia and hypercapnia produce severe erythrocytosis that causes a change in blood viscosity. This may facilitate thrombus formation at the lamina cribrosa of both eyes manifested as bilateral CRVO. RETINAL CASES & BRIEF REPORTS 3:140 –143, 2009
From the *Glaucoma Department and the †Retina Department, Asociacio´n para Evitar la Ceguera en Me´xico, México City, México.
sometimes associated with hyperviscosity syndromes. In these syndromes, balance, described by Virchow in the 19th century, is disrupted, causing vein occlusion.4 We describe a man with morbid obesity and recent bilateral visual loss; diagnosis, treatment, and follow-up are discussed.
O
besity– hypoventilation syndrome was first described in modern literature by Burwell et al,1 who based part of their observations on one of Dickens’ characters. The syndrome is defined using the following criteria: obesity (body mass index, ⬎30 kg/m2); diurnal sleepiness; hypercapnia (PaCO2, ⬎45 mmHg); and obstructive sleep apnea (apnea– hypopnea index, ⬎30 per hour) or severe oxygen desaturation.2 Patients with obesity– hypoventilation syndrome may also present with morning headaches, fatigue, polycythemia, pulmonary hypertension, and right-sided congestive heart failure (cor pulmonale). If untreated, morbidity and mortality are considerably increased.3 Central retinal vein occlusion (CRVO) is a well-known disease that is
Case Report A 37-year-old Hispanic man presented to our hospital complaining of an 8-day history of progressive bilateral visual loss. He also had trouble staying awake during his job, small effort dyspnea, headaches, and very short sleep cycles (5 hours). His medical history was notable for high blood pressure, deep venous insufficiency, and ecchymosis in the lower limbs. He had morbid obesity (weight, 151 kg; body mass index, 55 kg/m2). Best-corrected visual acuity was 20/130 in the right eye and 20/100 in the left eye. Intraocular pressure was 14 mmHg in both eyes. Results of anterior biomicroscopic examination were unremarkable. Ocular movements, pupil responses, and lens examination results were normal for both eyes. Fundus examination of both eyes revealed clear vitreous, hyperemic optic disk with poorly defined edges, flame hemorrhages in the posterior pole, massive venous dilation and tortuosity, and mild macular edema. The right
Reprint requests: Raul Velez-Montoya, Vicente Garcı´a Torres Number 46, San Lucas Coyoacan, Mexico DF 04060; e-mail: [email protected]
140
141
BILATERAL CRVO IN OBESITY–HYPOVENTILATION SYNDROME
Fig. 1. Color fundus photographs of the right (A) and left (B) eyes show a hyperemic disk with poorly defined edges, flame hemorrhages, and severe venous dilation and tortuosity. There is also a subhyaloid hemorrhage in the right eye. C and D, Fluorescein angiography shows a delayed filling time, with earlyphase disk hyperfluorescence and no evidence of vascular leakage.
A
B
C
D
posterior pole also had a sub hyaloid hemorrhage. Neither eye had clinical evidence of retinal neovascularization. Fluorescein angiography showed early-phase disk hyperfluorescence, delay in vascular filling time, and hypofluorescence due to retinal hemorrhages. Vascular shunts or leakage due to neovascularization was not seen (Fig. 1). Complete blood cell count determination showed an erythrocyte count of 8.01⫻102 cells per liter, hemoglobin level of 23.9 g/dL, and hematocrit of 81.1%. Leukocyte count and blood chemistry levels were within normal limits. At this point, a diagnosis of bilateral CRVO and erythrocytosis was made. Treatment was started with oral acetylsalicylic acid (100 mg once a day) and captopril (25 mg twice a day) and prophylactic phlebotomy. At the same time, the patient began treatment at the sleep clinic of Instituto Nacional de Enfermedades Respiratorias (Mexico), where additional studies were performed (chest roentgenography, cranial computed tomography, blood gas analysis, electrocardiography, and polysomnography). Results of chest roentgenography and cranial computed tomography were normal. The electrocardiogram showed signs of right ventricle hypertrophy. Blood gas analysis showed hypercapnia (PaCO2, 52 mmHg) with hypoxemia (blood oxygen saturation [SaO2], 54%). Polysomnography demonstrated 45 obstructive apneas and 133 obstructive hypopneas (apnea duration, 20.4 seconds) and abnormal movements of the inferior limbs during sleep. With this new evidence, we made the following diagnoses: sleep apnea syndrome with severe hypoxemia, erythrocytosis, blood hyperviscosity, and obesity– hypoventilation syndrome (pickwickian syndrome). Treatment was restarted with a strict weight-loss diet, supplementary oxygen (1 L/min) via a nasal mask, and continuous positive airway pressure of 18 centimeters of water. Two years later, best-corrected visual acuity was 20/20 in the right eye and 20/25 in the left eye. Arterial blood pressure was 130/80 mmHg, weight was 81 kg (body mass index, 30.4 kg/m2), SaO2 was 98 mmHg, and PaCO2 was 37 mmHg. The erythrocyte
count was 5.30⫻1012 cells per liter, hemoglobin level was 16.6 g/dL, and hematocrit was 48.0%. The rest of the laboratory findings were within normal limits. Fundus examination showed a normal yellow disk with well-defined edges, resolution of retinal hemorrhages, and vessels with a normal appearance. Fluorescein angiography revealed a normal vascular filling time and hyperfluorescence in the inferior peripapillary area due to choroidal transmission secondary to alterations in the retinal pigment epithelium with no signs of vascular leakage (Fig. 2). All clinical changes, blood pressure, weight, and visual acuity were maintained at the last follow-up (February 2007).
Discussion Blood hyperviscosity syndrome is one of the less common causes of CRVO. It is characterized by an increase in blood components that slows transit through blood vessels, causing formation of thrombi. Waldenstro¨m macroglobulinemia is the most frequent hyperviscosity syndrome.5 There have been many reports of cases in which an increase of circulating immunoglobulins, secondary to multiple myeloma or by iatrogenic therapeutic administration, produced a state of sanguineous hyperviscosity causing bilateral CRVO.6,7 Pickwickian syndrome is a disease characterized by morbid obesity, hypercapnia, hypoxia, and obstructive sleep apnea.3 To our knowledge, the only reported ophthalmologic manifestations associated with this syndrome are disk edema, which can be associated with intracranial hypertension,8 and bi-
142
A
C
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 2
B Fig. 2. Color fundus photographs of the right (A) and left (B) eyes 2 years after the first visit show clearance of flame hemorrhages and no signs of neovascularization. C, Fluorescein angiography shows early-phase hyperfluorescence in the inferior peripapillary area due to choroidal transmission and some hypofluorescent spots surrounded by a hyperfluorescent halo, which are believed to be alterations in the pigment epithelium (the patient never received laser treatment). Filling time was normal, and there was no evidence of vascular leakage. D, Normal fluorescein angiogram.
D
lateral iris neovascularization. The exact cause of these manifestations is not known. Nevertheless, it has been suggested that hypoxia and hypercapnia can promote abnormal secretion of vascular endothelial growth factor via a nonischemic mechanism. The specific pathways are not known.9 In the present case, hypoxia and hypercapnia produced severe erythrocytosis (erythrocyte count, 8.01 m/mL; hemoglobin level, 23.9 g/dL; hematocrit, 81.1%), causing a change in blood viscosity (most likely causing formation of a thrombus in the lamina cribrosa of both eyes manifested by bilateral CRVO). Because of the patient’s age, we had to rule out other possible etiologies, especially blood hypercoagulable states. Serum levels of homocysteine, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies were all within normal limits or negative.4 The alterations detected by polysomnography together with the other laboratory findings confirmed the diagnosis of obesity– hypoventilation syndrome (pickwickian syndrome), which responds favorably to weight loss therapy and mechanical ventilation. Another disease that must be ruled out is pseudotumor cerebri. It presents most frequently in obese women in their mid-20s to 30s. Common presenting signs are diplopia, cranial nerve palsies, nausea, vomiting, dizziness, neck stiffness, tinnitus, inferior limb paresthesias, and arthralgias. There is high opening
pressure when lumbar puncture is performed, with normal cerebrospinal fluid. We did not perform lumbar puncture in our case because all clinical and laboratory findings pointed to a retinal vascular condition rather than cranial hypertension.10 In the current case, clinical improvement of the fundus with supplemental oxygen administration with continuous positive airway pressure is notable. This case demonstrates that respiratory therapy with continuous positive airway pressure can be useful in the treatment of bilateral CRVO associated with obesity– hypoventilation syndrome. Key words: obesity– hypoventilation syndrome, pickwickian syndrome, central retinal vein occlusion, hyperviscosity, polycythemia. References 1.
2.
3. 4.
5.
Burwell CS, Robin ED, Whaley RD, Bickelmann AG. Extreme obesity associated with alveolar hypoventilation—a pickwickian syndrome. 1956. Obes Res 1994;2:390–397. Akashiba T, Akahosi T, Kawahara S, et al. Clinical characteristics of obesity-hypoventilation syndrome in Japan: a multi-center study. Intern Med 2006;45:1121–1125. Olson AL, Zwillich C. The obesity hypoventilation syndrome. Am J Med 2005;118:948–956. Lahey JM, Tunc¸ M, Kearney J, et al. Laboratory evaluation of hypercoagulable states in patients with central retinal vein occlusion who are less than 56 years of age. Ophthalmology 2002;109:126–131. Menke MN, Feke GT, McMeel JW, et al. Hyperviscosity-
BILATERAL CRVO IN OBESITY–HYPOVENTILATION SYNDROME
6.
7.
related retinopathy in Waldenstro¨m macroglobulinemia. Arch Ophthalmol 2006;124:1601–1606. Hayasaka S, Ugomori S, Kodama T, et al. Central retinal vein occlusion in two patients with immunoglobulin G multiple myeloma associated with blood hyperviscosity. Ann Ophthalmol 1993;25:191–194. Oh KT, Boldt HC, Danis RP. Iatrogenic central retinal vein occlusion and hyperviscosity associated with high-dose intravenous immunoglobulin administration. Am J Ophthalmol 1997;124:416–418.
8. 9.
10.
143
Wolin MJ, Brannon WL. Disk edema in an overweight woman. Surv Ophthalmol 1995;39:307–314. Duh EJ, Finkelstein D, Schneider T, et al. Bilateral iris neovascularization as the initial sign of obesity-hypoventilation (pickwickian) syndrome: hypoxia/hypercapnia as a stimulus for angiogenesis. Arch Ophthalmol 2000;118: 1298–1300. Chern S, Magargal LE, Brav SS. Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Ann Ophthalmol 1991;23:54–57.
