Diagnostic and Therapeutic Challenges
Edited by H. Richard McDonald
Drs. Diana A. Dmuchowska, Renata Zalewska, Malgorzata Jasiewicz, Pawel Krasnicki, Andrzej Mikita, Bozena Sobkowicz, Zofia Mariak, and David Sarraf
T
his case is submitted by Drs. Diana A. Dmuchowska, Renata Zalewska, Pawel Krasnicki, Andrzej Mikita, and Zofia Mariak of the Department of Ophthalmology, University Teaching Hospital of Bialystok, Bialystok, Poland, and Malgorzata Jasiewicz and Bozena Sobkowicz of the Department of Cardiology, University Teaching Hospital of Bialystok, Bialystok, Poland; commented by Dr. David Sarraf, Los Angeles, California.
Dr. David Sarraf (Los Angeles, California): This interesting case report describes a 62-year-old female patient with acute painless vision loss because of bilateral macular detachment manifesting as cystoid macular edema and foveal detachment with bilateral spectral domain OCT analysis. Pertinent macular history includes PAH and medical treatment with acetazolamide and sildenafil therapy. The differential diagnosis for exudative macular detachment is vast and includes malignant hypertension, but unfortunately, the authors fail to provide this systemic information. Given the patient’s age, toxemia of pregnancy that can be associated with high blood pressure and signs of disseminated intravascular coagulation is unlikely. Lupus choroidopathy may also be associated with exudative macular detachment. Other more common etiologies such as central serous retinopathy should also be considered, but this patient refused an intravenous angiogram. However, the patient’s demographic and the large short-term fluctuations of macular edema demonstrated in the OCT panel make this diagnosis unlikely. Inflammatory disorders such as Harada disease may be considered, but the color photographs and the OCT images are inconsistent with this diagnosis. Similarly, an optic nerve pit was not identified on analysis of the disk with the photographs provided. This patient has three relevant clues in her medical history. Pulmonary hypertension has been associated with macular edema and serous macular detachment without leakage on angiography. Retinopathy may also be identified with this disorder. It is possible that the patient’s diagnosis of PAH may be the etiology for the macular detachment, and this may have resolved with better systemic control. However, Elschnig spots have not been associated with PAH, although these were not well visualized with the color images provided. Moreover, there was no evidence of retinopathy.
Case Report A 62-year-old woman was referred because of sudden painless bilateral deterioration of visual acuity in the span of 2 days. She described dark spots in vision, color desaturation, and prolonged recovery from bright light. Her ophthalmologic history was negative, except for bilateral +2.0 diopter (D) sph hyperopia. The patient has been treated for pulmonary hypertension (PAH) for several years with phosphodiesterase-5 inhibitor (sildenafil citrate 3 · 20 mg), beta blocker (metoprolol), and calcium channel blocker (amlodipine). Serous foveal detachment and retinal edema were revealed on fundoscopy of the macular region, along with multiple round yellowish choroidal changes resembling Elschnig spots (Figure 1, top). The abnormalities were bilateral but more pronounced in the right eye. Apart from macular changes and dilated blood vessels in the conjunctiva, the patient’s ophthalmic examination yielded regular results, with proper color vision in both eyes. Spectral domain optical coherence tomography (OCT) (TOPCON 3D OCT-1000; Topcon Medical Systems Inc., Oakland, CA) imaging demonstrated bilateral serous foveal detachment (maximum height during follow-up: 929 mm in the right eye and 605 mm in the left eye) and cystoid edema of the outer retina (maximum retinal thickness during follow-up: 746 mm in the right eye and 478 mm in the left eye). The patient did not consent to further examination, which required administering intravenous contrast. Average thickness of the sclera was documented on sonography. Throughout the 9-month follow-up period, the patient’s bestcorrected visual acuity fluctuated in the range from 0.4 to 1.0 in the right eye and 0.7 to 1.0 in the left eye, with correction from +2.0 to 4.0 D sph depending on the height of the foveal detachment. This case is presented for diagnosis, mechanism of serous retinal detachment, additional workup, and treatment.
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2418 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Fig. 1. Color fundus photographs showing macular edema and Elschnig spots-like choroidal abnormalities (top). Horizontal OCT scans through the fovea, which illustrates bilateral serous foveal detachment, cystoid edema of the outer retina, and retinal pigment epithelium protrusions (middle). Color fundus photographs depicting retinal pigment epithelium mottling in the maculae of both eyes (bottom). BCVA, best-corrected visual acuity; LE, left eye; p.o., per os; RE, right eye.
2015 VOLUME 35 NUMBER 11
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
Interestingly, sildenafil can cause a congestive choroidopathy leading to macular edema. Unfortunately, choroidal imaging (enhanced depth imaging) was not provided, and therefore, a reliable interpretation of the choroid was not possible. Moreover, the macular detachment resolved while the patient was still receiving this therapy. Acetazolamide is a sulfur-containing medication that can cause uveal effusion and macular edema and macular folds, but typically myopia is induced. This patient is hyperopic, and therefore, acetazolamide is an unlikely explanation for the macular detachment. More likely, PAH is the etiology for the macular edema that resolved because of more optimal systemic control. Choroidal imaging windows to assess for an exudative choroidopathy would be especially important in this case and ruling out high blood pressure, as well as signs of lupus and disseminated intravascular coagulation would be very helpful to narrow the differential diagnosis. Editor’s Note: Drs. Dmuchowska, Zalewska, Jasiewicz, Krasnicki, Mikita, Sobkowicz, and Mariak have presented an unusual case of a 62-year-old woman with a rapid, painless, bilateral visual decrease. The OCT revealed bilateral serous foveal detachment. Dr. David Sarraf has consulted on this case and states that the differential diagnosis is vast but includes malignant hypertension, toxemia of pregnancy, disseminated intravascular coagulopathy, lupus choroidopathy, central serous retinopathy, Harada disease, and optic pit with retinal detachment. But, Dr. Sarraf believes that the answer lies in the patient’s medical condition, noting that PAH has been associated with macular edema and serous macular detachment without angiographic leakage. He states that congestive choroidopathy secondary to sildenafil may occur and believes that enhanced depth imaging would be of value in this regard. He discounts this mechanism, however, as the patient’s macular detachment resolved while the patient was on the drug. Dr. Sarraf concludes that the PAH is the etiology for the macular edema that resolved under better control. He encourages the presenters to perform choroidal imaging windows to assess for exudative choroidopathy, ruling out high blood pressure, as well as signs of lupus and disseminated intravascular coagulopathy. Follow-up: The patient has been treated for PAH for several years with phosphodiesterase-5 inhibitor (sildenafil 3 · 20 mg), beta blocker (metoprolol), and calcium channel blocker (amlodipine). She was classified as Class II (of 4) of PAH.
2419
A few cases of sildenafil-associated serous macular detachments that responded to drug discontinuation and reoccurred after reintroduction were previously reported.1,2 However, the indication for administering the drug was different (erectile dysfunction in males), and therefore, the data regarding the cause–effect relationship between sildenafil use and central serous chorioretinopathy is inconclusive. In their extensive controlled trial, Wirostko et al3 do not name this side effect. French and Margo4 and Azzouni and Abu Samra5 also contradict the view that phosphodiesterase-5 inhibitors increase the risk for central serous chorioretinopathy. As the association seemed unclear to us and we suspected sildenafil-related choroidopathy and retinopathy, sildenafil was discontinued and acetazolamide and nonsteroidal antiinflammatory drug were introduced, the former orally, the latter topically. This caused progress of PAH to Class IV (the most advanced). Only initial resolution of ophthalmic abnormalities with subsequent deterioration of retinal changes was observed (Figure 1). Sildenafil was reintroduced after 3 weeks because of significant worsening of PAH symptoms. This decision corresponded with temporary resolution of retinal changes, with their subsequent recurrence afterward, despite improvement of PAH to Class II. At the same time, acetazolamide was discontinued because of side effects (itchiness). A case of PAH-related serous macular detachment responsive to acetazolamide treatment was reported in the literature.6 During further follow-up, spontaneous fluctuations, and finally, improvement of visual acuity, fundus, and OCT findings were observed in our patient. Significant resolution of OCT abnormalities has been noted after 9 months, with almost complete reabsorption of the subretinal fluid with a tiny space left between the retinal pigment epithelium and neurosensory retina, normalization of retinal thickness, and foveal contour restoration, accompanied by full visual acuity. Thus, evident retinal pigment epithelium protrusions modeling the photoreceptor layer were noted. These images confirmed funduscopic findings of multiple pigment clumpings surrounded by yellow halo in the place of former Elschnig-like spots. Macular abnormalities resembling Elschnig spots reflect the lobular pattern of the choriocapillaris suggestive of choroidal ischemia. We hypothesize that underlying vascular disease (PAH) leads to choroidal hypoperfusion and serous detachment of the retina, with concomitant ischemia of the outer retinal layers resulting in cystoid edema. We thank the presenters for their case and follow-up and Dr. Sarraf for his analysis.
2420 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
References 1. Fraunfelder FW, Fraunfelder FT. Central serous chorioretinopathy associated with sildenafil. Retina 2008;28:606–609. 2. Quiram P, Dumars S, Parwar B, Sarraf D. Viagra-associated serous macular detachment. Graefes Arch Clin Exp Ophthalmol 2005;243:339–344. 3. Wirostko BM, Tressler C, Hwang LJ, et al. Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension. BMJ 2012;344:e554. 4. French DD, Margo CE. Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study. Retina 2010;30:271–274. 5. Azzouni F, Abu Samra K. Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A
2015 VOLUME 35 NUMBER 11
critical analysis and review of the literature. J Sex Med 2011; 8:2894–2903. 6. Hammond CJ, Chauhan DS, Stanford MS. Pulmonary hypertension and diffuse macular edema responsive to acetazolamide. Arch Ophthalmol 1998;116:1535–1536.
RETINA, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
Edited by H. Richard McDonald
Drs. Diana A. Dmuchowska, Renata Zalewska, Malgorzata Jasiewicz, Pawel Krasnicki, Andrzej Mikita, Bozena Sobkowicz, Zofia Mariak, and David Sarraf
T
his case is submitted by Drs. Diana A. Dmuchowska, Renata Zalewska, Pawel Krasnicki, Andrzej Mikita, and Zofia Mariak of the Department of Ophthalmology, University Teaching Hospital of Bialystok, Bialystok, Poland, and Malgorzata Jasiewicz and Bozena Sobkowicz of the Department of Cardiology, University Teaching Hospital of Bialystok, Bialystok, Poland; commented by Dr. David Sarraf, Los Angeles, California.
Dr. David Sarraf (Los Angeles, California): This interesting case report describes a 62-year-old female patient with acute painless vision loss because of bilateral macular detachment manifesting as cystoid macular edema and foveal detachment with bilateral spectral domain OCT analysis. Pertinent macular history includes PAH and medical treatment with acetazolamide and sildenafil therapy. The differential diagnosis for exudative macular detachment is vast and includes malignant hypertension, but unfortunately, the authors fail to provide this systemic information. Given the patient’s age, toxemia of pregnancy that can be associated with high blood pressure and signs of disseminated intravascular coagulation is unlikely. Lupus choroidopathy may also be associated with exudative macular detachment. Other more common etiologies such as central serous retinopathy should also be considered, but this patient refused an intravenous angiogram. However, the patient’s demographic and the large short-term fluctuations of macular edema demonstrated in the OCT panel make this diagnosis unlikely. Inflammatory disorders such as Harada disease may be considered, but the color photographs and the OCT images are inconsistent with this diagnosis. Similarly, an optic nerve pit was not identified on analysis of the disk with the photographs provided. This patient has three relevant clues in her medical history. Pulmonary hypertension has been associated with macular edema and serous macular detachment without leakage on angiography. Retinopathy may also be identified with this disorder. It is possible that the patient’s diagnosis of PAH may be the etiology for the macular detachment, and this may have resolved with better systemic control. However, Elschnig spots have not been associated with PAH, although these were not well visualized with the color images provided. Moreover, there was no evidence of retinopathy.
Case Report A 62-year-old woman was referred because of sudden painless bilateral deterioration of visual acuity in the span of 2 days. She described dark spots in vision, color desaturation, and prolonged recovery from bright light. Her ophthalmologic history was negative, except for bilateral +2.0 diopter (D) sph hyperopia. The patient has been treated for pulmonary hypertension (PAH) for several years with phosphodiesterase-5 inhibitor (sildenafil citrate 3 · 20 mg), beta blocker (metoprolol), and calcium channel blocker (amlodipine). Serous foveal detachment and retinal edema were revealed on fundoscopy of the macular region, along with multiple round yellowish choroidal changes resembling Elschnig spots (Figure 1, top). The abnormalities were bilateral but more pronounced in the right eye. Apart from macular changes and dilated blood vessels in the conjunctiva, the patient’s ophthalmic examination yielded regular results, with proper color vision in both eyes. Spectral domain optical coherence tomography (OCT) (TOPCON 3D OCT-1000; Topcon Medical Systems Inc., Oakland, CA) imaging demonstrated bilateral serous foveal detachment (maximum height during follow-up: 929 mm in the right eye and 605 mm in the left eye) and cystoid edema of the outer retina (maximum retinal thickness during follow-up: 746 mm in the right eye and 478 mm in the left eye). The patient did not consent to further examination, which required administering intravenous contrast. Average thickness of the sclera was documented on sonography. Throughout the 9-month follow-up period, the patient’s bestcorrected visual acuity fluctuated in the range from 0.4 to 1.0 in the right eye and 0.7 to 1.0 in the left eye, with correction from +2.0 to 4.0 D sph depending on the height of the foveal detachment. This case is presented for diagnosis, mechanism of serous retinal detachment, additional workup, and treatment.
2417
2418 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
Fig. 1. Color fundus photographs showing macular edema and Elschnig spots-like choroidal abnormalities (top). Horizontal OCT scans through the fovea, which illustrates bilateral serous foveal detachment, cystoid edema of the outer retina, and retinal pigment epithelium protrusions (middle). Color fundus photographs depicting retinal pigment epithelium mottling in the maculae of both eyes (bottom). BCVA, best-corrected visual acuity; LE, left eye; p.o., per os; RE, right eye.
2015 VOLUME 35 NUMBER 11
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
Interestingly, sildenafil can cause a congestive choroidopathy leading to macular edema. Unfortunately, choroidal imaging (enhanced depth imaging) was not provided, and therefore, a reliable interpretation of the choroid was not possible. Moreover, the macular detachment resolved while the patient was still receiving this therapy. Acetazolamide is a sulfur-containing medication that can cause uveal effusion and macular edema and macular folds, but typically myopia is induced. This patient is hyperopic, and therefore, acetazolamide is an unlikely explanation for the macular detachment. More likely, PAH is the etiology for the macular edema that resolved because of more optimal systemic control. Choroidal imaging windows to assess for an exudative choroidopathy would be especially important in this case and ruling out high blood pressure, as well as signs of lupus and disseminated intravascular coagulation would be very helpful to narrow the differential diagnosis. Editor’s Note: Drs. Dmuchowska, Zalewska, Jasiewicz, Krasnicki, Mikita, Sobkowicz, and Mariak have presented an unusual case of a 62-year-old woman with a rapid, painless, bilateral visual decrease. The OCT revealed bilateral serous foveal detachment. Dr. David Sarraf has consulted on this case and states that the differential diagnosis is vast but includes malignant hypertension, toxemia of pregnancy, disseminated intravascular coagulopathy, lupus choroidopathy, central serous retinopathy, Harada disease, and optic pit with retinal detachment. But, Dr. Sarraf believes that the answer lies in the patient’s medical condition, noting that PAH has been associated with macular edema and serous macular detachment without angiographic leakage. He states that congestive choroidopathy secondary to sildenafil may occur and believes that enhanced depth imaging would be of value in this regard. He discounts this mechanism, however, as the patient’s macular detachment resolved while the patient was on the drug. Dr. Sarraf concludes that the PAH is the etiology for the macular edema that resolved under better control. He encourages the presenters to perform choroidal imaging windows to assess for exudative choroidopathy, ruling out high blood pressure, as well as signs of lupus and disseminated intravascular coagulopathy. Follow-up: The patient has been treated for PAH for several years with phosphodiesterase-5 inhibitor (sildenafil 3 · 20 mg), beta blocker (metoprolol), and calcium channel blocker (amlodipine). She was classified as Class II (of 4) of PAH.
2419
A few cases of sildenafil-associated serous macular detachments that responded to drug discontinuation and reoccurred after reintroduction were previously reported.1,2 However, the indication for administering the drug was different (erectile dysfunction in males), and therefore, the data regarding the cause–effect relationship between sildenafil use and central serous chorioretinopathy is inconclusive. In their extensive controlled trial, Wirostko et al3 do not name this side effect. French and Margo4 and Azzouni and Abu Samra5 also contradict the view that phosphodiesterase-5 inhibitors increase the risk for central serous chorioretinopathy. As the association seemed unclear to us and we suspected sildenafil-related choroidopathy and retinopathy, sildenafil was discontinued and acetazolamide and nonsteroidal antiinflammatory drug were introduced, the former orally, the latter topically. This caused progress of PAH to Class IV (the most advanced). Only initial resolution of ophthalmic abnormalities with subsequent deterioration of retinal changes was observed (Figure 1). Sildenafil was reintroduced after 3 weeks because of significant worsening of PAH symptoms. This decision corresponded with temporary resolution of retinal changes, with their subsequent recurrence afterward, despite improvement of PAH to Class II. At the same time, acetazolamide was discontinued because of side effects (itchiness). A case of PAH-related serous macular detachment responsive to acetazolamide treatment was reported in the literature.6 During further follow-up, spontaneous fluctuations, and finally, improvement of visual acuity, fundus, and OCT findings were observed in our patient. Significant resolution of OCT abnormalities has been noted after 9 months, with almost complete reabsorption of the subretinal fluid with a tiny space left between the retinal pigment epithelium and neurosensory retina, normalization of retinal thickness, and foveal contour restoration, accompanied by full visual acuity. Thus, evident retinal pigment epithelium protrusions modeling the photoreceptor layer were noted. These images confirmed funduscopic findings of multiple pigment clumpings surrounded by yellow halo in the place of former Elschnig-like spots. Macular abnormalities resembling Elschnig spots reflect the lobular pattern of the choriocapillaris suggestive of choroidal ischemia. We hypothesize that underlying vascular disease (PAH) leads to choroidal hypoperfusion and serous detachment of the retina, with concomitant ischemia of the outer retinal layers resulting in cystoid edema. We thank the presenters for their case and follow-up and Dr. Sarraf for his analysis.
2420 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES
References 1. Fraunfelder FW, Fraunfelder FT. Central serous chorioretinopathy associated with sildenafil. Retina 2008;28:606–609. 2. Quiram P, Dumars S, Parwar B, Sarraf D. Viagra-associated serous macular detachment. Graefes Arch Clin Exp Ophthalmol 2005;243:339–344. 3. Wirostko BM, Tressler C, Hwang LJ, et al. Ocular safety of sildenafil citrate when administered chronically for pulmonary arterial hypertension: results from phase III, randomised, double masked, placebo controlled trial and open label extension. BMJ 2012;344:e554. 4. French DD, Margo CE. Central serous chorioretinopathy and phosphodiesterase-5 inhibitors: a case-control postmarketing surveillance study. Retina 2010;30:271–274. 5. Azzouni F, Abu Samra K. Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? A
2015 VOLUME 35 NUMBER 11
critical analysis and review of the literature. J Sex Med 2011; 8:2894–2903. 6. Hammond CJ, Chauhan DS, Stanford MS. Pulmonary hypertension and diffuse macular edema responsive to acetazolamide. Arch Ophthalmol 1998;116:1535–1536.
RETINA, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
