A 50-year-old Caucasian male presented to the emergency department, complaining of sudden vision loss and the presence of scotoma in his left eye (OS) with no ocular pain or discomfort. His past ophthalmic history was unremarkable. The patient had a history of painful anal fissure under treatment with GTN 0.2% ointment three times daily for the previous 2 months. After almost every application of the ointment, he was symptomatic with headache and dizziness that were partially relieved by common analgesics. He also reported that during the previous 15 days, pain from the fissure was significantly stronger, especially after bowel movement, which caused him to apply the ointment more often (up to 6 times daily). During the last 3 days, he reported episodes of transient postural hypotension. He was under no other medications and reported only occasional consumption of caffeine. He had no history of smoking, excessive drinking, or substance abuse.
Best-corrected visual acuity (BCVA) was 85 ETDRS letters OD and 75 ETDRS letters OS. Intraocular pressure was within normal limits. RAPD was negative in both eyes, and Ishihara plates showed no apparent dyschromatopsia. Anterior chamber examination of both eyes was unremarkable. There were no significant fundoscopic findings OD. Fundoscopy OS revealed mild retinal venous dilatation and tortuosity with scattered blot hemorrhages (Figures 1(a) and 1(b)). In the outer retina, subtle, parafoveal, whitish lesions were noted. Extensive multimodal imaging which included OCT, fundus autofluorescence (FAF), optical coherence tomography-angiography (OCT-A), and fluorescein angiography (FA) was performed (Figures 1(c)-1(h)).
Swept-source-optical coherence tomography (DRI OCT Triton, SS-OCT) demonstrated diffuse, hyperreflective lesions at the level of the inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) compatible with Paracentral Acute Middle Maculopathy (PAMM, Figures 2(a) and 2(b)). Fundus autofluorescence did not reveal any hyper- or hypofluorescent lesions of the Retinal Pigment Epithelium (RPE). Optical coherence tomography-angiography (DRI OCT Triton, SS-OCT) revealed a focal, small area of capillary dropout in the deep capillary plexus. Superficial capillary plexus, outer retina, and choriocapillaris appeared normal. No other vascular abnormalities were apparent. Fluorescein angiography revealed normal arteriovenous transit time, masking effect due to blot hemorrhages, and early punctuate leakage in the inner retina (Figure 3).
An extensive haematological workup which included complete blood count, fasting blood sugar and hemoglobin A1c, ESR, CRP, LDL, HDL, plasma homocysteine level, rheumatoid factor, ANA, ANCA, SACE, FTA-ABS, VDRL, antiphospholipid antibodies, protein C and S levels, factor V Leiden, cryoglobulins and a thrombophilia screen was performed. Moreover, plasma protein electrophoresis, chest X-ray (for the exclusion of sarcoidosis, tuberculosis, and left ventricular hypertrophy), and a magnetic resonance angiography (for any vascular stenosis) with contrast dye were also performed. The patient was also referred to cardiology for a full assessment with electrocardiogram, carotid Doppler imaging, cardiac echocardiogram, and rhythm and blood pressure Holter monitoring. There was no cardiological or vascular disease diagnosed. Haematological workup, X-ray, and MRA revealed no pathological findings.
The patient was advised to immediately discontinue any application of the drug. During the following month, the patient did not experience any of his previous symptoms and his visual acuity OS was 80 ETDRS letters with no RAPD. Fundoscopy revealed partial resolution of blot hemorrhages. The macula appeared normal. OCT revealed retinal disruption and thinning at the level of INL and OPL and partial resolution of the hyperreflective lesions (Figure 2(c)). OCT-A remained unaltered (Figure 1(i)).
Six months later, the patient was free of symptoms. Visual acuity OS was 80 ETDRS letters. Fundoscopy revealed complete resolution of the hemorrhages and the whitish lesions (Figure 1(j)). OCT showed INL and OPL thinning and complete resolution of the hyperreflective lesions (Figure 2(d)).
The patient mentioned that 8 months after the initial diagnosis, he had an exacerbation of symptoms regarding his anal fissure. He applied the ointment twice during a day for 4 days, which led to the remission of headaches and transient reduction of his visual acuity. He discontinued the drug application.