High-Risk Histopathological Features of Retinoblastoma following Primary Enucleation: A Global Study of 1426 Patients from 5 Continents.

PURPOSE: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents. METHODS: Retrospective study of 1426 primarily enucleated RB eyes from five continents. RESULTS: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients. CONCLUSION: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA.

Electroretinographic changes in the inner and outer retinal layers before and after intravenous chemotherapy for retinoblastoma.

PURPOSE: To study the inner and outer retinal functions using a full-field electroretinogram (ERG) before and after intravenous chemotherapy (IVC) in children with retinoblastoma (RB). METHODS: Of the 11 eyes, seven had RB and four were normal. All children were examined under anesthesia using a handheld ERG machine with a standard protocol - light-adapted single-flash ERG (fERG), photopic single-flash 3.0- and 30-Hz flickers, and photopic negative response (PhNR) amplitudes at 72 ms (P72). The amplitudes and peak times were compared before and after IVC. RESULTS: Post-chemotherapy tumor regressed in all seven eyes. Of the seven eyes, the fERG peak time (a-wave) was delayed in two eyes (29%), whereas the b-wave was delayed in six eyes (86%). The fERG amplitude height for a- and b-waves decreased in five eyes (71%) and six eyes (86%), respectively. In addition, photopic flicker 30-Hz b-wave peak time delayed in five eyes (71%), whereas the b-wave amplitude height decreased in six eyes (86%). Simultaneously, the P72 amplitude height decreased in six eyes (86%), whereas the P-ratio increased in all seven eyes (100%). In comparison, the ERG responses improved in three of the four contralateral normal eyes. Overall, the cone function improved in two eyes (29%), whereas cone bipolar cell and retinal ganglion cell (RGC) function improved in one eye (14%) each. CONCLUSION: Comparison of light-adapted ERG changes before and after IVC showed reduced amplitudes and delayed peak times for both a and b waveforms, as well as reduced PhNR amplitude attributable to bipolar and RGC injury.

Ultrasound Biomarkers: Contrast-enhanced Ultrasound and Nakagami Imaging to Differentiate Benign and Malignant Choroidal Tumor.

PURPOSE: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions. METHODS: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied. RESULTS: CEUS analysis showed that the time-averaged estimated contrast was significantly higher (p = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM (p = 0.001 for CH cases and p < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher (p = 0.032) for CH (m = 0.61) than for CM (m = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher (p = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM. CONCLUSIONS: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions.

Evolving criteria for group E retinoblastoma: impact on outcomes.

OBJECTIVE: To assess the impact of evolving criteria for group E retinoblastoma on ocular survival outcomes. DESIGN: A retrospective observational study. METHODS: Single-institution consecutive case series of patients with advanced intraocular retinoblastoma (groups D and E) were classified based on International Intraocular Retinoblastoma Classification (IIRC) and International Classification of Retinoblastoma (ICRB) criteria. The main outcomes measured were ocular survival, frequency of histopathologic risk factors (HRF), and the need for adjuvant therapy. RESULTS: A total of 332 eyes of 298 patients were classified into group D (150, 45%) and E eyes (182, 55%) based on IIRC criteria. ICRB classification resulted in upstaging of 57 group D eyes (17%) to group E. Eyes that were upstaged to group E from D in the ICRB classification (E1) differed significantly, with a greater proportion undergoing primary enucleation (17 of 57, 30%) than those that were not (10 of 93, 11%) (p = 0.003). Similar significant differences were observed between group E2 and E3 eyes (p < 0.0001). Ocular survival according to Kaplan-Meier estimates at 12 months of 79%, 59%, 49%, and 1% differed significantly between all groups (ICRB D, E1, E2, and E3, respectively). CONCLUSION: Proposed new subgrouping of group E eyes into E1, E2, and E3 based on clinical criteria is based upon natural history of tumor progression and is predictive of ocular survival. Preservation of the existing lower boundaries for group E by ICRB and IIRC offers the possibility of reanalyzing existing published data.

Ruthenium-106 (106Ru) plaque brachytherapy for treatment of circumscribed choroidal hemangioma.

PURPOSE: To describe the clinical and imaging features of circumscribed choroidal hemangiomas (CCH) and their treatment outcomes with Ruthenium-106 (106Ru) plaque brachytherapy. METHODS: Retrospective study of 24 patients (24 eyes) diagnosed with CCH and treated with 106Ru plaque between 2017 and 2022. Analysis included pre- and post-treatment clinical and imaging features such as tumor regression, reduction in height, subretinal fluid (SRF) resolution, and change in best-corrected visual acuity (BCVA). RESULTS: The mean age at presentation was 36 years (range, 16-57). The most common tumor location was the temporal quadrant (n = 19) with macular involvement (n = 13). Associated features were macular SRF (n = 22) and inferior exudative retinal detachment (n = 10). Nineteen of the 24 patients underwent primary treatment, whereas 5 patients underwent plaque as a salvage treatment. The mean tumor apex dose was 40 Gy. At a median follow-up of 7.5 months (range 3-65 months), 18 eyes showed complete regression, whereas 6 eyes showed partial regression. The mean height decreased from 4.8 (SD 1.28) mm at presentation to 2.5 (SD 1.63) mm. Median BCVA improved from logMAR 1.2 (IQR 0.4-2) at baseline to logMAR 1.05 (IQR 0.1-1.95) (p = 0.4). Complete resolution of the macula and tumor SRF was observed in 15 (68%) and 13 (57%) eyes, respectively. The radiation-related complications observed were radiation maculopathy (4 eyes), retinopathy (1 eye), and vitreous hemorrhage (1 eye). CONCLUSION: Ruthenium-106 plaque brachytherapy is effective for CCH (> 3 mm height) as a primary and salvage treatment for tumors unresponsive to other modalities.

Advanced intraocular retinoblastoma: evolving criteria for group E disease.

With evolving criteria for classifying intraocular retinoblastoma (RB) from International Intraocular Retinoblastoma Classification (IIRC, 2005) to International Classification of Retinoblastoma (ICRB, 2006), there have been changes in the inclusion criteria for groups E eyes that have not been widely recognized. This brief review highlights issues with the current classification systems (ICRB and IIRC) and layouts a theoretical framework arguing for merging of 2 existing classifications into 1 and subdividing the expanded group E RB, thereby preserving the possibility to reanalyze existing published data.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

PURPOSE: To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). METHODS: A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). RESULTS: Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). CONCLUSION: Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Management of retinoblastoma: are we there yet?

Since the introduction of intraarterial chemotherapy (IAC) in the last decade, there has been a paradigm shift in the management of retinoblastoma (RB), especially in developed countries. Despite improved globe salvage outcomes with IAC compared with systemic intravenous chemotherapy, IAC has certain limitations, such as poor accessibility and affordability, especially for middle- and low-income countries; the need for expertise; local ocular complications; and possible increased risk of systemic metastasis. This review discusses the important limitations of the current treatment strategy of using IAC, as well as the prospects of new therapeutic targets or routes of drug delivery that may lead to further improvements in the management of RB.

Occlusive retinal vasculitis as a presenting feature of primary vitreoretinal lymphoma relapse.

PURPOSE: To report a case of primary vitreoretinal lymphoma (PVRL) relapse presenting as occlusive retinal vasculitis with secondary neovascularization. MATERIALS AND METHODS: A retrospective case report. RESULTS: A Forty-year-old woman presented to the clinic with complaints of blurring of vision in the left eye for 4 months. Her best corrected visual acuity (BCVA) was 20/20 and 20/500 in the right and left eye, respectively. Both eyes' vitreous cavities showed vitreous opacities (2+). Both eyes fundus showed multifocal yellowish-white subretinal infiltration. A diagnostic vitreous and subretinal biopsy of the left eye revealed large lymphoid cells with CD20 positivity, confirming the diagnosis of PVRL. The patient received twelve intravitreal methotrexate (MTX) injections in both eyes over a course of 2 months, following which the lesions completely resolved. However, after 5 months, the left eye showed characteristic subretinal lesions along with perivascular exudates and retinal haemorrhages, diagnosed as PVRL relapse presenting as occlusive retinal vasculitis. Fluorescein angiography revealed retinal neovascularization (NVE), for which pan-retinal photocoagulation was performed along with repeated intravitreal MTX injection. CONCLUSION: PVRL is a great masquerader, and although rare, PVRL relapse can present as occlusive retinal vasculitis with secondary NVE, thereby delaying diagnosis and subsequent treatment.

Metastatic retinoblastoma at presentation: Clinical presentation, treatment, and outcomes.

The aim of this study was to retrospectively determine clinical features, treatment outcomes, and overall survival in four patients with metastatic retinoblastoma at presentation. The mean age at diagnosis was 63 months (range: 24-108 months). Three patients had overt orbital disease of at least one eye and one patient had microscopic orbital disease with scleral infiltration on histopathology. Metastatic sites included regional lymph nodes (RLN) (n = 4), bone marrow (BM) (n = 2), and cerebrospinal fluid (CSF) (n = 1). The most common sites of RLN were ipsilateral preauricular nodes (two patients) and contralateral parotid gland involvement (one patient). The treatment administered included primary enucleation (n = 1), high-dose intravenous chemotherapy (n = 4), secondary enucleation (n = 2), orbital external beam radiotherapy (n = 3), and intrathecal chemotherapy (n = 1). High-risk features included massive choroidal and microscopic scleral infiltration in the eye that underwent primary enucleation. At a mean follow-up of 33 months (range, 4-68 months), one patient with CSF involvement deceased in 4 months. The remaining three patients were alive and disease-free at the last mean follow-up period of 43 months (range, 18-68 months). The results of our study showed that RLN and BM metastasis respond well to treatment while CSF metastasis is associated with poor prognosis.

Multifocal choroidal melanoma: a clinicohistopathological correlation.

A woman in her late 50s presented with on-and-off redness and diminution of vision in her left eye for 6 months. Her best corrected visual acuity was 20/40 in the right eye and hand motion in the left eye. Anterior segment examination revealed a greyish-white lesion extending from 3 to 6 o'clock hours posterior to the iris and protruding into the anterior chamber. Left eye B-scan ultrasonography showed a multifocal choroidal lesion, a smaller one involving the posterior pole, and a larger lesion involving the complete nasal quadrant and anteriorly extending to the ciliary body and iris. Fine-needle aspiration biopsy performed from the anterior lesion showed a possible neoplastic aetiology of melanocytic origin of the cells. Finally, the patient underwent left eye enucleation with a ball implant. Histopathological examination of the enucleated eye confirmed the final diagnosis of multifocal choroidal melanoma involving the adjacent ciliary body and iris.

Surgical and visual outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma.

Purpose: We evaluated the anatomical and functional outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma (RCH). Methods: This was a retrospective case series of 15 patients (16 eyes) with tractional or combined retinal detachment (RD) managed with pars plana vitrectomy and tumor endoresection (ER) with/without feeder vessel ligation. Results: The mean age at the time of surgery was 30 years (range, 14-46 years). The most common tumor locations were inferotemporal (six eyes) and temporal (six eyes) quadrants. Indications for surgery included exudative RD with fibrovascular proliferation (eight eyes), combined RD (five eyes), vitreous hemorrhage (four eyes), and rhegmatogenous RD (two eyes). Tumor destruction was performed with laser and/or cryotherapy in nine eyes (57%) and ER in seven eyes (43%). Feeder vessel was ligated and cauterized in 10 (63%) and six eyes (37%), respectively. Anatomical success after initial surgery was 50% (eight eyes), which improved to 88% (14 eyes) after they underwent a repeat procedure for recurrent RD (eight eyes). At the last visit, visual acuity improved in seven eyes (44%), was stable in four eyes (25%), and worsened in five eyes (31%) with a mean follow-up of 29 months (6-79 months). Comparison between the ER group and the laser/cryotherapy group revealed no significant difference in final retinal reattachment rate (89% vs. 86%, P > 0.05), with better visual outcomes in laser/cryotherapy group (57% vs. 78%, P < 0.05). Conclusion: Pars plana vitrectomy with/without tumor endoresection can be a safe and effective treatment option for complex RCHs, achieving good tumor control and anatomical success with limited functional success.

High-resolution imaging of the whole eye with photoacoustic microscopy.

Observation and characterization of any changes in anatomical structures of ocular components remain as a conventional technique for diagnosis, staging, therapeutic treatments, and post-treatment monitoring of any ophthalmic disorders. The existing technologies fail to provide imaging of all of the various components of the eye simultaneously at one scanning time, i.e., one can recover vital patho-physiological information (structure and bio-molecular content) of the different ocular tissue sections only one after another. This article addresses the longstanding technological challenge by use of an emerging imaging modality [photoacoustic imaging (PAI)] in which we integrated a synthetic aperture reconstruction technique (SAFT). Experimental results-with experiments being conducted in excised tissues (goat eye)-demonstrated that we can simultaneously image the entire structure of the eye (∼2.5 cm) depicting clearly the distinctive ocular structures (cornea, aqueous humor, iris, pupil, eye lens, vitreous humor, and retina). This study uniquely opens an avenue for promising ophthalmic (clinical) applications of high clinical impact.

GIANT RETINAL TEAR DETACHMENT: Clinical Presentation and Treatment Outcomes in 396 Patients.

PURPOSE: To study etiology, clinical presentation, anatomical, and functional outcomes of patients with giant retinal tear detachment at a tertiary eye institute. METHODS: Retrospective, consecutive case series of 396 patients (396 eyes) who underwent surgery were reviewed. Factors affecting the final anatomical and functional success were determined. RESULTS: Mean age was 37 years (range; 1-79 years), and 86% (n = 339) of the subjects were men. Trauma (21%) and high myopia (11%) were predisposing risk factors. Two hundred and seventy-seven eyes (70%) had giant retinal tear configuration of >180° and <270°, associated with partial retinal detachment in 282 (71%) eyes and macular detachment in 262 (66%) eyes. Primary surgery included pars plana vitrectomy (n = 240, 61%), pars plana vitrectomy with encirclage band (n = 152, 38%), or scleral buckle (n = 4, 1%). The mean follow-up duration was 15 months (median, 8.4 months; range, 3-83 months). Anatomical success after initial surgery was 64% (255 eyes), which improved to 78% (308 eyes) after undergoing a second vitreoretinal procedure for recurrent retinal detachment (53 eyes). Median visual acuity improved from 20/1,500 preoperatively to 20/400 at final follow-up ( P = 0.01), and 15% of eyes achieved postoperative visual acuity of 20/60 or better. Factors associated with poor anatomical success included age <16 years ( P = 0.005) and presenting visual acuity 20/400 or less ( P = 0.001). CONCLUSION: Trauma and myopia constituted the major risk factors for giant retinal tear detachment in our series. Surgery for giant retinal tear detachment managed with pars plana vitrectomy with or without encirclage band and silicone oil tamponade had good anatomical and favorable visual outcomes at last follow-up.

Vasoproliferative retinal tumors: Clinical presentation and treatment outcome.

OBJECTIVE: To study the clinical presentation and treatment outcomes of patients with vasoproliferative retinal tumor (VPRT) in India. METHODS: Retrospective study of 50 eyes in 47 patients. RESULTS: Of the 50 eyes, 25 (50%) were primary and 25 (50%) were secondary. Common ocular pathologies related to secondary VPRT included retinal detachment (n = 8, 32%) and Coats disease (n = 7, 28%). Overall, the mean age at presentation was 35 years (range; 3-74 years) and included 30 (64%) males and 17 (36%) females. The lesions were unilateral in 44 (94%) patients. Secondary retinal features included intra/subretinal exudation (n = 41, 82%), vascularity (n = 32, 64%), subretinal fluid (n = 21, 42%), retinal neovascularisation (n = 9, 18%) and vitreous hemorrhage (n = 8, 16%). Thirty-four eyes (68%) underwent cryotherapy, of which 16 eyes (47%) received adjunct intravitreal anti-VEGF (12 eyes) or corticosteroid injection (4 eyes). Primary surgery included vitrectomy with/without encirclage and cryotherapy (n = 12, 24%) and plaque brachytherapy (n = 3, 6%). At last follow-up (mean 9.7 months, range 3-67 months), 42 eyes (84%) had complete tumor regression with no improvement in visual outcomes when comparing presenting and final best corrected visual acuity. Comparing primary versus secondary VPRT, secondary VPRT presented a decade earlier (31 vs 40 years), needed surgical intervention (48% vs 20%), had poor tumor control (72% vs 92%) and worse visual outcomes (p < 0.05). CONCLUSION: VPRTs commonly present as a unilateral lesions in the adult population with equal prevalence of primary and secondary variants. Compared with primary VPRT, secondary VPRTs require surgical treatment and are associated with poor visual outcome.

Coats disease in India: clinical presentation and outcome in 675 patients (690 Eyes).

PURPOSE: To study the clinical profile, treatment, and visual outcome of patients with Coats disease in India. METHODS: This was a cross-sectional, observational hospital-based study of patients diagnosed with Coats disease during a 10-year period using an electronic medical record system. RESULTS: We identified 675 patients with Coats disease with a prevalence rate of 0.025%. The mean age of the patients was 16.8 years (median, 12 years). Majority were males (75%) with unilateral presentation (98%) in first decade of life (n = 309, 46%). The most common presentation was foveal exudation (stage 2B, n = 161, 23.3%), followed by exudative retinal detachment-extrafoveal (stage 3A1, n = 143, 20.7%), and extrafoveal exudation (stage 2A, n = 136, 19.7%). Treatment modalities included observation (48 eyes, 17%), laser photocoagulation ± intravitreal bevacizumab/triamcinolone acetonide (n = 82, 29%), cryotherapy ± intravitreal bevacizumab/triamcinolone acetonide (n = 64, 23%), and surgical intervention (n = 86, 31%). Despite appropriate treatment, at mean follow-up of 16 months, there was no significant difference between presenting and final visual acuity (48% vs. 48%, p > 0.05). Using multivariate regression analysis, factors associated with poor visual outcome were younger age (< 0.001; - 0.02 to - 0.1), unilateral disease (0.04; - 0.68 to - 0.01), cataract (0.004; 0.13 to 0.69), retinal detachment (< 0.001; 0.49 to 0.82), and glaucoma (< 0.001; 0.34 to 0.94). CONCLUSION: The most common clinical presentation of Coats disease in India is foveal exudation in first and second decade. At initial presentation, about half of the affected eyes had blindness and one-third underwent surgical intervention.

Primary Subretinal Seeding in Retinoblastoma: Clinical Presentation and Treatment Outcomes.

Introduction: The aim of this study was to describe the clinical features and treatment outcomes of primary subretinal seeding (SRS) in patients with intraocular retinoblastoma (RB). Methods: Descriptive analysis of primary SRS in 47 patients (50 eyes) with RB was performed. Results: Mean age was 19 months (range, 2-72 months), and 55% (n = 26) of the subjects were male. At presentation, the SRS involved two or more quadrants in 88% of eyes. Most seeds appeared yellowish gray (66%) and round to oval in shape (48%). Two-thirds of SRS were seen posterior to the equator and within 5 mm from the main tumor. Associated features included subretinal fluid in 50 eyes (100%), total retinal detachment in 28 eyes (56%), and vitreous seeds in 20 eyes (40%). Treatment included intravenous chemotherapy (IVC) (n = 47; 94%), enucleation (n = 2; 4%), and intra-arterial chemotherapy (n = 1; 2%). SRS treatment included adjunct use of focal transpupillary thermotherapy and/or cryotherapy (n = 20; 40%). Retinal tumor control was achieved in 36 eyes (76%) with 32 eyes (78%) showing a type 3 regression pattern, while SRS completely regressed in 24 (48%) eyes, partially in 15 (30%) and worsened in 2 (4%) eyes. Over a mean follow-up of 30 months (range, 3-68 months), SRS recurrence was noted in 12 eyes (29%), globe salvage was achieved in 39 eyes (78%), and 1 (4%) patient died of presumed metastasis. Conclusion: Primary SRS pose a therapeutic challenge during RB treatment. The SRS responds moderately to systemic IVC, with one-third cases showing SRS recurrence and one-fifth ultimately requiring enucleation.

Internal limiting membrane detachment in acute Central Retinal Artery Occlusion: clinical features, multimodal imaging, outcomes & prognostic biomarker.

PURPOSE: To report the clinical features, multi-modal imaging characteristics and their corroboration, and prognostic value of internal limiting membrane detachment (ILMD), a novel OCT biomarker in acute CRAO. DESIGN: Retrospective observational case-control study at institutional tertiary eye care centers. METHODS: 60 eyes of 60 patients of acute CRAO with optical coherence tomography (OCT) at baseline were included. Eyes were grouped in (a) With ILMD; (b) With no-ILMD. Multimodal imaging correlation, BCVA change and binary logistic regression were studied. RESULTS: Eighteen eyes (30%) were noted to have ILMD. At presentation, ILMD on OCT corroborated with macular non-perfusion with enlarged foveal avascular zone both on OCT-angiography (OCTA) and fundus fluorescein angiography (FFA). On follow-up, ILMD had resolved in all cases with fragmentation, disruption and atrophy of the retinal layers. Logistic regression showed poor baseline visual acuity was significantly associated with the odds of ILMD [Odds Ratio (OR) 31.02, p = 0.0018, 95% confidence interval: 1.81-529] while controlling for potential confounders including age (p = 0.60), gender (p = 0.316) duration of symptoms (p = 0.114), follow-up duration (p = 0.450) and final BCVA (p = 0.357). Eyes with ILMD and no-ILMD had a baseline BCVA of 2.62 LogMAR (light perception) and 2.05 LogMAR (Snellen equivalent 20/2000), respectively. On follow up, none of the eyes with ILMD showed any improvement. In contrast, nine (21.4%) eyes in no-ILMD had a vision of 20/400 and above with a mean final visual acuity of 1.87 + 0.78 LogMAR (p = 0.000). CONCLUSION: ILMD correlated with macular non-perfusion and poor baseline visual acuity which showed no improvement on follow-up, suggesting it to be poor prognostic biomarker.

Primary central nervous system lymphoma: Inter-compartmental progression.

There is limited understanding of the inter-compartmental progression and treatment outcomes of primary central nervous system lymphoma (PCNSL). In this multicenter retrospective cohort study on 234 patients with PCNSL (median age: 62.5 years [18-92]; median follow-up 35 months [0.1-237.0]) from 2000 till 2018 were divided into group 1 (ocular, 44 patients): 1A and 1B without and with CNS progression and group 2 (CNS, 190 patients): 2A and 2B without and with ocular progression, respectively. In group 1 (44 patients), 33 patients received local treatment, and 11 patients received systemic treatment. In group 2 (15 patients), six patients received combination treatment, while seven patients received only systemic treatment. A complete response was observed in 19 (43%) and 91 (48%) patients in groups 1 and 2, respectively. The 2-year progression-free survival (PFS) was 35% (95% CI: 0.23, 0.54) and 56% (95% CI: 0.49, 0.63) for groups 1 and 2, respectively (p < 0.0001). Age < 60 years was significantly associated with longer PFS (median PFS 48 vs. 24 months, p = 0.01). The overall survival (OS) at 2-year was similar among groups 1 and 2 (83% and 67%), respectively (p = 0.06). Thus, Initial compartment of involvement does not influence local response rate or OS.

Aqueous humor as a surrogate biomarker for retinoblastoma tumor tissue.

PURPOSE: To demonstrate the feasibility of identifying a germline RB1 pathogenic variant in retinoblastoma (RB) from an aqueous humor (AH) sample. METHODS: In this pilot case series, peripheral blood, fresh tumor tissue, and AH were obtained from 3 eyes of 3 RB patients who underwent enucleation at a tertiary eye care institute. After isolation of the cell-free DNA (cfDNA), sequence analysis of the RB1 core promoter and of exons 1 through 27, including nearby flanking intronic regions, was performed using a custom targeted hybridization protocol, followed by high-throughput sequencing. RESULTS: The study cohort included 3 enucleated eyes with advanced RB (group E [n = 2], group D [n = 1]). In case 1, deletion of the RB1 promoter to exon 23 (delP->23) on both alleles was identified from tumor as well as AH samples and absent in the blood sample, indicative of absence of a germline RB1 pathogenic variant. In case 2, two heterozygous RB1 nonsense variants, c.610G>T p.(Glu204Ter) and c.751C>T p.(Arg251Ter), were identified in tumor and AH samples (allele frequency of 49% and 45%, resp.) and were absent in the blood sample, indicative of absence of a germline RB1 pathogenic variant. In case 3, a heterozygous c.2326-14T>A substitution on allele 1 and loss of heterozygosity on allele 2 were identified in the tumor and AH (allele frequency of 97%), with the same heterozygous mutation in the blood sample, indicating presence of a germline RB1 pathogenic variant. CONCLUSIONS: The pathogenic RB1 variant results from AH in all 3 eyes were concordant with direct tumor DNA sampling, suggesting that AH can serve as a surrogate for tumor tissue. Because the AH can be accessed during treatment, specific testing can be performed even in the absence of enucleation.