Perifoveal exudative vascular anomalous complex (PEVAC) resembling lesion in a patient with multiple myeloma.

Purpose: To report a case of a perifoveal exudative vascular anomalous complex (PEVAC) resembling lesion in a patient with multiple myeloma. Observations: A 56-year-old male with multiple myeloma presented with sudden moderate vision loss in the right eye. Best-corrected visual acuity was 20/25 in his right eye. Fundus examination showed a vascular irregularity in the perifoveal region. Fluorescein angiography (FA) revealed an isolated perifoveal aneurysmal lesion with minimal leakage. On optical coherence tomography (OCT) examination, a large oval structure with a hyperreflective wall and exudation was visualised. Three weeks later, spontaneous improvement of the intraretinal fluid was observed on OCT without treatment. However, 3 months later the macular edema recurred. The appearance of the aneurysmal lesion is similar to a PEVAC lesion, which is an isolated well-defined perifoveal intraretinal vascular abnormality presenting on OCT as a round hyperreflective structure with a dark lumen containing variably reflective material and is commonly associated with cystic intraretinal fluid. Conclusions and Importance: PEVAC was originally described as occurring in healthy patients, but recent observations suggest that it also appears in association with other retinal/choroidal vascular abnormalities or underlying cardiovascular abnormalities. Our case supports this hypothesis by demonstrating a PEVAC resembling lesion in a patient with multiple myeloma.

RESOLUTION OF CHOROIDAL METASTASIS AND ASSOCIATED SUBRETINAL EXUDATION OF METASTATIC CUTANEOUS MELANOMA 15 DAYS AFTER TREATMENT WITH COMBINED TARGETED THERAPY.

PURPOSE: To report a case of metastatic cutaneous melanoma to the choroid with rapid and complete resolution of associated choroidal elevation and subretinal fluid after initiation of combined targeted therapy. METHODS: We describe a case of a 41-year-old man diagnosed with a metastatic cutaneous melanoma to the choroid of his right eye, for which treatment with dabrafenib/trametinib was initiated. RESULTS: A 41-year-old man with a past medical history of a BRAF V600E/V600E2/V600D mutated invasive superficial spreading cutaneous melanoma presented with acute metamorphopsia and blurred vision in his right eye. Examination revealed a best-corrected visual acuity (BCVA) of 20/22 and 2 elevated choroidal lesions temporal to the fovea with subretinal exudation to the fovea on fundoscopy. On repeat examination 3 days later, his vision had further decreased to 20/50 with an increase of subretinal fluid. Treatment with BRAF/MEK-inhibitor dabrafenib/trametinib was initiated, with complete resolution of the choroidal masses and subretinal exudation and improvement of the BCVA to 20/22 after only 15 days. Follow-up 8 weeks after start of therapy showed stable fundoscopic and tomographic findings, with further improvement of BCVA to 20/17 and no ocular side effects. CONCLUSION: A case of metastatic cutaneous melanoma to the choroid with choroidal elevation and subretinal exudation to the fovea, for which treatment with dabrafenib/trametinib was initiated. Rapid and complete resolution of choroidal metastasis and the associated subretinal exudation after initiation of combined targeted therapy was seen, without any ocular side effects.

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial.

CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.

The corneoscleral shape in Marfan syndrome.

PURPOSE: To investigate the corneoscleral shape in Marfan syndrome (MFS) patients. METHODS: Thirty eyes of 15 participants with molecularly proven MFS were included in this prospective, cross-sectional study. Optical biometry, Scheimpflug imaging, and corneoscleral topography (Eye Surface Profiler) were performed in all patients. Topographic data were compared to data from controls (25 emmetropes and 17 myopes). The raw three-dimensional anterior height data from MFS eyes and control eyes were exported for further analysis. Custom-made software was used to demarcate the limbal radius and to calculate the sagittal height in different concentric annuli centred at the corneal apex, placed in a pupil plane, for the central cornea (0-4 mm radius), peripheral cornea (4-6 mm radius) and sclera (6-8 mm radius) and the corneoscleral asymmetry. RESULTS: Marfan syndrome (MFS) eyes had significantly lower values of mean sagittal height compared to non-MFS eyes in all three annuli (central cornea, corneal periphery and sclera (independent t-test, p < 0.01 except for the inferior area of the scleral radius: p > 0.05). The sclera was significantly more asymmetric in MFS eyes compared to myopes (independent t-test, p < 0.01 for both eyes), but similar to emmetropes (independent t-test, p = 0.17 and p = 0.93 for right and left eyes, respectively). In MFS eyes, scleral asymmetry was not found to be correlated with axial length (Pearson correlation coefficient, r < 0.30, p > 0.05). CONCLUSION: The peripheral cornea and sclera of Marfan syndrome patients have a significantly different shape compared to healthy controls.

Bilateral Corneal Graft Rejection Associated With Pembrolizumab Treatment.

PURPOSE: To report the first case of corneal graft rejection presumably associated with pembrolizumab immunotherapy. METHODS: Case report and literature review. RESULTS: An asymptomatic 85-year-old woman with a history of bilateral penetrating keratoplasty presented for a follow-up visit with bilateral diffuse keratic precipitates and subepithelial infiltrates. There were no anterior chamber cells. Bilateral subclinical corneal graft rejection was suspected. Three months previously, pembrolizumab immunotherapy was started for a metastatic urothelial cell tumor. Corneal graft rejection was managed with topical dexamethasone drops, which were tapered slowly. Pembrolizumab treatment was continued with careful ophthalmological follow-up. Unfortunately, recurrence of corneal graft rejection was observed 8 weeks after cessation of topical dexamethasone drops. After consulting the treating oncologist, pembrolizumab treatment was stopped to prevent recurrent corneal graft rejection. CONCLUSIONS: We report the first case of corneal graft rejection presumably associated with pembrolizumab immunotherapy. Corneal graft rejection may be successfully managed with corticosteroid therapy. However, constant vigilance and follow-up are advised because of the risk of recurrence in case of continued pembrolizumab treatment. Given the subclinical presentation, baseline ophthalmological screening is advised in all corneal graft patients after initiating immune checkpoint inhibitor therapy.