Multimodal imaging characteristics in eyes with vitreoretinal lymphoma treated with intravitreal rituximab.

PURPOSE: To characterize the imaging features in eyes with vitreoretinal lymphoma (VRL) using ultra-widefield fundus photography (UWF-FP), swept-source optical coherence tomography (SSOCT) and fundus autofluorescence (FAF) that are correlated to ongoing treatment with intravitreal Rituximab(IVR). METHODS: Retrospective observational imaging-based study of 15 treatment-naive eyes with VRL treated with IVR. All patients with primary VRL underwent vitreous biopsy using 23/25G microincision vitrectomy system for confirmation of diagnosis. All eyes received monthly IVR (1 mg/0.1 mL) injections till disease remission. Baseline clinical characteristics, treatment details, outcomes, and sequential imaging features on UWF-FP, FAF, and SSOCT were analyzed. OUTCOME MEASURES: Baseline features and changes in UWF-FP, FAF patterns, and SSOCT features in response to treatment RESULTS: Clinically, patients presented with sub-RPE deposits (n = 15), superficial retinal hemorrhages (n = 2), 'giant' RPE (retinal pigment epithelium) holes (n = 2), and anterior segment reaction (n = 1). Eyes were treated with mean 5.7 IVR injections (median: 5; range 1-13) over a mean 7.2 ± 4.9 months. During the course of treatment, two eyes developed superficial retinal hemorrhages with spontaneous resolution, 2 eyes developed CME, and 4 eyes developed characteristic 'leopard skin' pigmentation. Hyper-autofluorescence corresponding to areas of active lesions decreased with each treatment cycle and was finally replaced by hypo-autofluorescence. Serial OCTs showed regression of sub-RPE/subretinal deposits (n = 15), ellipsoid zone disruption (n = 9), and its resolution with treatment (n = 3), epiretinal membrane (ERM; n = 6), choroidal hyperreflective foci (HRF; n = 4), disorganization of retinal inner layers (DRIL; n = 3), RPE-rip (n = 2), cystoid macular edema (CME; n = 2), and hyperreflective lesions in the choroid (n = 1). Complete resolution was observed in all eyes with extensive hypo-AF. The central foveal thickness decreased from 237 ± 113 µ to 182 ± 114 µ (p = 0.1) and subfoveal choroidal thickness decreased from 258 ± 66 µ to 220 ± 64 µ (p = 0.12) at final follow-up. The mean baseline BCVA was logMAR 0.9 ± 0.9 that deteriorated to mean logMAR 1 ± 1 final visit (p = 0.7). The mean recurrence-free follow-up was 5.9 ± 5.1 months CONCLUSION: Multimodal imaging provides novel insights into features of VRL, a better understanding of regression patterns, and prognostication of outcomes when treated with intravitreal rituximab. Larger, multicentric studies with longer follow-up will help unravel imaging biomarkers to understand these aspects better.

Intravitreal rituximab monotherapy for management of eyes with vitreoretinal lymphoma: initial experience from India.

PURPOSE: To evaluate treatment outcomes and complications of intravitreal rituximab (IVR) monotherapy for eyes with vitreoretinal lymphoma (VRL). METHODS: Patients diagnosed with 'isolated primary VRL' or 'VRL with remission of systemic disease' and treated with IVR (1 mg/0.1 ml) between June 2014 and June 2019 were included in this retrospective, interventional case series. Injections were repeated at monthly intervals until complete resolution. All patients signed a written informed consent form. Institutional review board approval was obtained. RESULTS: Twelve eyes of 7 patients with VRL were treated with 77 IVR injections at mean 6.42 injections per eye (median = 5; range = 2-13) for complete resolution at mean 8.16 ± 4.62 months (median = 6.97 months; range = 1.97-14.33 months). Mean age at presentation was 53.3 years (median = 54 years; range = 34-74 years). Patients were co-managed with medical oncologist and periodically evaluated. Complications included anterior uveitis (n = 6), raised intraocular pressure (n = 3), posterior synechiae (n = 2), vitreous haemorrhage (n = 1), pre-retinal haemorrhage (n = 1), retinal detachment (n = 1), posterior subcapsular cataract (n = 2) and sectoral iris atrophy (n = 1). Recurrences were seen in 3 eyes (25%), which eventually achieved complete resolution with treatment. None of the patients had systemic involvement or death during follow-up. Mean follow-up was 18.73 ± 8.83 months (median = 21.60 months; range = 7.37-32.67 months). CONCLUSION: Intravitreal rituximab monotherapy is effective in management of vitreoretinal lymphoma in patients with isolated ocular disease.

Vitreous Seed Classification and Regression Patterns in Eyes With Retinoblastoma.

Purpose: This work subclassifies retinoblastoma vitreous seeds and evaluates the efficacy, regression patterns, and adverse effects of combination intravitreal melphalan and topotecan chemotherapy for resistant and recurrent vitreous seeds. Methods: A retrospective review of medical records was conducted of patients with retinoblastoma and resistant or recurrent vitreous seeds who were treated with intravitreal melphalan and topotecan injections from August 2014 to July 2018. Main outcome measures included regression pattern, time for regression, time for recurrence of seeds, treatment outcomes, and ocular toxicity. Results: Nineteen eyes received 138 intravitreal injections over 74 treatment sessions (mean, 7.26 injections per eye); vitreous seeds regressed in 18 eyes. Of cloud vitreous seeds, curvilinear (n = 2) and sphero-linear (n = 2) subtypes were observed. During regression, some sphere seeds showed an intermediary streak-like pattern and took longer to regress (mean, 11.13 ± 14.05 months and 11.67 ± 8.62 injections) than those without the intermediary streak-like pattern (mean, 3.55 ± 2.57 months and 4.2 ± 1.87 injections). Mean follow-up was 34.87 ± 21.09 months (median, 35 months; range, 11-96 months). Anterior segment toxicity was seen in 10 (53%) eyes and posterior segment toxicity in 5 (26%) eyes. Kaplan-Meier survival estimates for globe salvage at 2 years was 94% and 73% at 5 years. Kaplan-Meier survival for vitreous seed-free status was 94% at 2 years and 65% at 5 years. Conclusions: An expanded vitreous seed classification system that further subcategorizes hitherto unrecognized vitreous seed morphology is needed. An intermediate streaking process results in a prolonged regression time for sphere vitreous seeds.

CERKL mutation causing retinitis pigmentosa(RP) in Indian population - a genotype and phenotype correlation study.

BACKGROUND: Mutations in CERKL gene has been reported to cause Retinitis pigmentosa (RP) and clinically appears discrete from other commonly encountered phenotypes. We report 14 patients who were seen to have CERKL mutation of the 152 patients of RP from Indian population who underwent genetic testing. MATERIALS AND METHODS: A retrospective analysis was performed in 28 eyes of the 14 unrelated patients to establish genotype phenotype correlation. Targeted next generation sequencing was performed using the STRAND® NGS v2.5 software. Validation was done using PCR-based bidirectional Sanger sequencing. Clinical data was collected along with imaging such as fundus photo, autofluorescence(AF), Optical coherence tomography and Electroretinogram wherever available. RESULTS: Three variants c.1045_1046delAT, c.847 C > T and a novel c.899-IG>A were identified. Retinal morphological features were typically bilaterally symmetrical with mild to moderate disc pallor and arteriolar attenuation in all cases, while sparse peripheral pigmentation was noted in seven patients indicating paucipigmentary character. Early macular involvement in all cases was a characteristic finding with central hypo-autofluorescence and surrounding hyper-autofluorescence. Peripheral scalloped chorioretinal atrophic patches were seen in five patients particularly in older patients. CONCLUSIONS: Phenotype associated with CERKL mutation appears clinically discrete from other commonly encountered phenotypes of inherited retinal dystrophies. Recognizing this typical genotype phenotype correlation will help clinicians to identify this form of RP, prognosticate the disease and segregate candidates for futures gene therapy.

Retinopathy of prematurity treatment: Asian perspectives.

Retinopathy of prematurity (ROP) is a vasoproliferative disease of developing retinal vessels that affects premature infants and can lead to severe and irreversible visual loss if left untreated. India and some other Asian countries are in the middle of a 'third ROP epidemic'. Blindness due to ROP is largely preventable if appropriate, adequate and accessible screening programmes are available. Screening of the premature babies is the first step in ROP management. With the increase in use of tele-screening techniques, more premature babies have been brought under the screening network both from urban and rural regions. Laser photocoagulation to the avascular retina using indirect ophthalmoscopy delivery system is the gold standard for ROP treatment and is usually done under topical anaesthesia in the Asian region in contrast to the western world. Use of intravitreal anti-vascular endothelial growth factors (VEGF) although controversial in management of ROP has been found to be effective in various Asian studies as well. ROP surgery in India and other middle-income Asian countries is largely performed only in few tertiary eye care centres. Poor visual prognosis, late presentation with advanced retinal detachments, lack of adequate number of trained paediatric retinal surgeons and paediatric anaesthetists also contribute to this problem. This current paper summarizes the Asian experience of ROP management.