Heterozygous RB1 mutation enhanced ATP production in human iPSC-derived retinal organoids.

BACKGROUND: Recent in vitro studies using RB1+/- fibroblasts and MSCs have shown molecular and functional disruptions without the need for biallelic loss of RB1. However, this was not reflected in the recent in vitro studies employing RB1+/- retinal organoids. To gain further insights into the molecular disruptions in the RB1+/- retinal organoids, we performed a high throughput RNA sequencing analysis. METHODS AND RESULTS: iPSCs were generated from RB1+/+ and RB1+/- OAMSCs derived from retinoblastoma patients. RB1+/+ and RB1+/- iPSCs were subjected to a step-wise retinal differentiation protocol. Retinal differentiation was evaluated by Real-time PCR and flow cytometry analysis of the retinal markers. To gain further insights into the molecular differences in RB1+/- retinal organoids, a high throughput RNA sequencing followed by differential gene expression analysis and gene set enrichment analysis (GSEA) was performed. The analysis revealed a shift from the regular metabolic process of glycolysis to oxidative phosphorylation in the RB1+/- retinal organoids. To investigate further, we performed assays to determine the levels of pyruvate, lactate and ATP in the retinal organoids. The results revealed significant increase in ATP and pyruvate levels in RB1+/- retinal organoids of day 120 compared to that of the RB1+/+. The results thus revealed enhanced ATP production in the RB1+/- retinal organoids. CONCLUSION: The study provides novel insights into the metabolic phenotype of heterozygous RB1 mutant suggesting dysregulation of energy metabolism and glycolytic pathways to be first step even before the changes in cellular proliferation or other phenotypic consequences ensue.

The Quantitative Detection of Cystatin-C in Patient Samples Using a Colorimetric Lateral Flow Immunoassay.

A colloidal gold-based lateral flow immunoassay was developed for the rapid quantitative detection of Cystatin-C in serum and whole blood. This device has an assay time of 15 min, making it a convenient point-of-care diagnostic tool. The device has a quantification range spanning from 0.5 to 7.5 µg/mL, with a lower limit of detection at 0.18 µg/mL. To validate its accuracy, the test was compared to a standard nephelometric immunoassay, and the results exhibited a robust linear correlation with an adjusted r2 value of 0.95. Furthermore, the device demonstrates satisfactory levels of analytical performance in terms of precision, sensitivity, and interference, indicating its potential for precise Cystatin-C quantification, particularly in renal-failure patients. Notably, the Cystatin-C-LFA device also demonstrates satisfactory stability, as a 30-day accelerated stability study at 50 °C showed no change in the device performance, indicating a long shelf life for the product when stored at room temperature.

Clinical spectrum and clinicopathological correlation of pediatric orbital tumors: 20 years' experience from a tertiary eye care center.

PURPOSE: To study the epidemiological profile of various pediatric orbital tumors and determine their clinicopathological correlation over 20 years. METHODS: A retrospective analysis of all pediatric patients with orbital tumors from the medical records between 1995 and 2015 was done. Tumors were categorized based on their cellular origin. Demographic details, clinical and histopathological diagnoses, frequency, and clinicopathological correlation were studied. RESULTS: A total of 265 pediatric patients with orbital tumors were analyzed, of which 145 (54.7%) patients were males and 120 (45.3%) were females. The mean age was 7 years (median: 6 years; range: 10 days-16 years). The distribution of lesions in each group was as follows: vasculogenic, 76 (28.7%); lipogenic and myxoid, 66 (25%); myogenic, 31 (11.7%); optic nerve and meningeal, 22 (8.3%); lymphoid and lymphoproliferative, 18 (6.8%); secondary orbital tumors, 14 (5.2%); histiocytic, 9 (3.4%); miscellaneous, 9 (3.4%), lacrimal gland, 8 (3%); mesenchymal with neural differentiation, 6 (2%); osseous, 4 (1.5%), and fibrocystic, 2 (0.8%). The most common benign and malignant pediatric orbital tumors were dermoid cysts (65, 24.5%) and rhabdomyosarcoma (31, 11.7%). A statistically significant ( P < 0.0001) clinicopathological correlation was observed in 208 (83.2%) out of 250 biopsy-proven cases. CONCLUSION: Pediatric orbital neoplasms include a broad spectrum of benign and malignant lesions. Vasculogenic tumors constitute the majority of them, followed by lipogenic and myxoid tumors. A thorough knowledge of the incidence, clinical profile, imaging features, and histopathology of specific orbital tumors aids in accurate diagnosis and their successful management.

A rare case of lacrimal sac dirofilariasis confirmed by polymerase chain reaction.

A 69-year-old female presented with complaints of persistent watering in the left eye for the past 8 years. She underwent a left external dacryocystorhinostomy (DCR) 8 years ago. On examination, left lacrimal passage irrigation showed regurgitation of fluid from opposite punctum. She underwent a revision external DCR with bicanalicular intubation and a portion of fibrosed sac was sent for histopathological examination (HPE). HPE showed a Microfilarial worm with surrounding granulomatous inflammation. Polymerase chain reaction (PCR) on the DNA extracted from the specimen identified the species to be Dirofilaria repens. Dirofilariasis is an accidental zoonotic infection in humans. Due to its migration, the worm can affect ocular and periocular structures. There are two case reports of perilacrimal dirofilariasis. This is the first case to report a filarial worm in the lacrimal sac causing chronic inflammation which probably led to failure of DCR. Treatment of choice is the complete eradication of the worm. PCR aids in the identification of species.

Advancements in Intraoperative Near-Infrared Fluorescence Imaging for Accurate Tumor Resection: A Promising Technique for Improved Surgical Outcomes and Patient Survival.

Clear surgical margins for solid tumor resection are essential for preventing cancer recurrence and improving overall patient survival. Complete resection of tumors is often limited by a surgeon's ability to accurately locate malignant tissues and differentiate them from healthy tissue. Therefore, techniques or imaging modalities are required that would ease the identification and resection of tumors by real-time intraoperative visualization of tumors. Although conventional imaging techniques such as positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), or radiography play an essential role in preoperative diagnostics, these cannot be utilized in intraoperative tumor detection due to their large size, high cost, long imaging time, and lack of cancer specificity. The inception of several imaging techniques has paved the way to intraoperative tumor margin detection with a high degree of sensitivity and specificity. Particularly, molecular imaging using near-infrared fluorescence (NIRF) based nanoprobes provides superior imaging quality due to high signal-to-noise ratio, deep penetration to tissues, and low autofluorescence, enabling accurate tumor resection and improved survival rates. In this review, we discuss the recent developments in imaging technologies, specifically focusing on NIRF nanoprobes that aid in highly specific intraoperative surgeries with real-time recognition of tumor margins.

Congenital orbital fibrosis: report of two cases and review of literature.

A 7-year-old male child presented with complaints of lagophthalmos and lid retraction of the right eye since birth. Magnetic resonance imaging (MRI) showed diffuse thickening of right superior rectus and levator-palpebrae complex along with a hypointense, irregular, and ill-defined lesion in the adjoining fat abutting the lacrimal gland. Biopsy from the lesion showed diffuse orbital fibrosis. Another 3-year-old female child presented with complaints of her right eye appearing smaller and inability to move the right eye freely since birth. MRI showed thickening of right superior and medial recti with diffuse retrobulbar hypointense fibrotic strands. The findings were suggestive of orbital fibrosis. Congenital orbital fibrosis is an extremely rare orbital pathology with very few cases described in the literature. The most common clinical features are motility restriction, restrictive strabismus, upper lid retraction, enophthalmos, and proptosis. The diagnosis can be made on imaging but requires biopsy for confirmation. Management is mostly conservative in the form of refractive and amblyopia therapy.

Bilateral Ocular Rosai-Dorfman Disease Presenting as Diffuse Anterior Scleritis with Multiple Enlarging Epibulbar Masses.

PURPOSE: To report a unique case of extranodal Rosai-Dorfman disease (RDD) presenting as bilateral scleritis, which progressed to multifocal epibulbar masses. METHODS: Retrospective chart review. RESULTS: A 35-year-old Asian man presented with progressive pain and redness in both eyes for 4 months. Examination revealed bilateral diffuse scleral congestion and areas of scleral thinning. The cornea and anterior chamber of each eye were unremarkable. Despite oral corticosteroid and immunosuppressive treatment, scleritis progressed to multifocal epibulbar masses. Tissue biopsy specimens revealed foamy macrophages with histiocytes staining positive for CD68 and S100, confirming a diagnosis of RDD. Systemic evaluation was unremarkable for lymphadenopathy or extranodal involvement. The patient was started on systemic chemotherapy and at last follow up after 1 year, all epibulbar lesions were completely resolved. CONCLUSIONS: Rosai-Dorfman disease can present as bilateral scleritis initially and develop epibulbar masses without any systemic involvement. Biopsy with immunohistochemical analysis can aid in the diagnosis.

Clinical and histopathological profile of primary caruncular lesions.

Purpose: To provide a retrospective analysis of lesions of the caruncle which have been very rarely reported in the literature. Methods: A retrospective review of all the caruncular lesions between January 2000 and January 2020 was done at a single tertiary eye care hospital. The lesions were classified as benign and malignant lesions. Clinicopathological correlation was done for the excised lesions. Results: A total of 87 caruncular lesions were included in the study. Males (59%) were affected more than females (41%). The mean age at presentation was 44 ± 20 years. The mean duration of complaint was 36 ± 62 months. A total of 36 patients underwent surgical excision whereas the rest opted for conservative management. Recurrence was noted in five patients. Fifteen different types of lesions were identified histopathologically. Benign lesions (78%) were far more common than malignant ones (22%). Epithelial inclusion cyst was the most common benign lesion and sebaceous gland carcinoma was the most common malignant lesion. Correct clinicopathological correlation was seen in 52.7% of the cases. Caruncular tuberculosis, oncocytoma, and basosquamous cell carcinoma were some of the rare lesions. Conclusion: Caruncular lesions are uncommon and very diverse, which makes clinical diagnosis challenging. Epithelial inclusion cyst and sebaceous gland carcinoma were the most common benign and malignant lesions respectively. Correct clinicopathological correlation was seen in more than half of the cases.

Dual-sensitive fluorescent nanoprobes for detection of matrix metalloproteinases and low pH in a 3D tumor microenvironment.

The overexpression of matrix metalloproteinases and low extracellular pH are two key physiological parameters involved in cancer initiation, progression, and metastasis. These have been the targets for several cancer detection and imaging modalities. Here, dual-sensitive nanoprobes have been fabricated from carbon nanoparticles decorated with a MMP-9 sensitive peptide sequence. Carbon nanoparticles are known for their intrinsic fluorescence properties and hence used as a pH-sensing moiety in the nanoprobes. In addition to this, selective-cleavage of the peptide sequence by MMP-9 results in the generation of a fluorescence signal due to separation of the quencher molecule from the fluorophore attached onto the MMP-9 sensitive peptide sequence, resulting in its detection. This protease-specific activation of the nanoprobes helps in precise tumor environment detection and imaging. The nanoprobes were thoroughly characterized for their chemical, physical and biological activities. The potential of these dual-sensitive nanoprobes to distinguish tumor-like microenvironments (low pH and elevated MMP-9 levels) from non-cancerous ones was evaluated in vitro in 2D cell culture as well as in 3D microscaffolds. The fluorescence microscopy images obtained in both in vitro systems revealed that low pH and high MMP-9 levels could be successfully visualised using these dual-sensitive nanoprobes. Therefore, these nanoprobes would find potential applications as a non-invasive imaging tool for visualising tumor margins in real-time.

Multicenter Evaluation of Diagnostic Circulating Biomarkers to Detect Sight-Threatening Diabetic Retinopathy.

Importance: It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR). Objective: To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR. Design, Setting, and Participants: This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4. Exposures: Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay. Main Outcomes and Measures: Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c. Results: A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data). Conclusions and Relevance: Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

Retinoblastoma patient-derived stem cells-an in vivo model to study the role of RB1 in adipogenesis.

Retinoblastoma (RB1) protein is a multifunctional protein that plays an important role in cell cycle regulation and cell differentiation, including adipogenesis. A detailed literature search to understand the role of RB1 in adipogenesis revealed that the nature of the RB1 inactivation (in vivo/in vitro) led to differences in adipogenesis. The majority of these studies were animal-based, and the only study in humans employed an in vitro mode of RB1 inactivation. To overcome these differences and lack of human studies, we sought to explore the role of RB1 in adipogenesis using orbital adipose mesenchymal stem cells (OAMSCs) from patients with retinoblastoma that innately carry a heterozygous RB1 mutation. We hypothesized that these patient-derived RB1 mutant OAMSCs can model in vivo RB1 inactivation in humans. Our study revealed increased adipogenesis with a bias toward brown adipogenesis in the RB1 mutant in addition to an increased number of adipocytes in the mitotic phase.

The effect of direct cell injury inflicted by cryotherapy on eyelid sebaceous gland carcinoma cells: An ex-vivo experimental study.

PURPOSE: To evaluate the effect of direct cell injury of cryotherapy on eyelid sebaceous gland carcinoma cells by an ex vivo cryotherapy experiment. METHODS: It was a prospective interventional case series. Six patients with biopsy-proven nodular sebaceous gland carcinoma were included. After excision of the mass, a thin slice of the mass resembling the thickness of the conjunctiva was shaved off and was oriented over the broad end of a tissue forceps. Cryotherapy was applied to both its anterior and posterior aspects by the triple freeze-thaw technique. The mass was then labeled and sent separately for histopathological evaluation by fixation and staining. RESULTS: A total of six patients with a mean age of 58.2 ± 15.5 years were included. There were four females and two males. The mean duration of the lesion was 21.6 ± 17.51 months. All patients had involvement of the upper eyelid. The patients were clinically staged as T2b (n=2), T1a (n=2), T2c (n=1), and T3a (n=1) respectively. There was no regional lymphadenopathy or metastasis in any of the cases. The experimental cryo-tissue containing the cryo-treated lesion revealed the presence of viable tumor cells (>50%) in all six specimens. CONCLUSION: The direct cell injury caused by cryotherapy may not be sufficient to kill all the residual sebaceous gland carcinoma cells on the tumor bed.

Primary apocrine adenocarcinoma of the lacrimal sac: an extremely rare variant of lacrimal sac neoplasm.

A 52-year-old male presented with right eye prominence of 1-year duration. Right eye examination revealed proptosis and limitation of extraocular movements. Magnetic resonance imaging (MRI) of the orbit showed soft tissue mass in the inferomedial orbit with medial rectus involvement and involving lacrimal sac. The patient underwent an incisional biopsy. Histopathology confirmed a diagnosis of primary orbital adenocarcinoma. Positron emission tomography computed tomography (PET CT) did not show the involvement of any other organ. Right orbital exenteration was done for disease control. On histopathology the mass was found to be arising from the lacrimal sac and was reported as apocrine adenocarcinoma. The diagnosis was further confirmed by immunohistochemistry with the tumor staining positive for gross cystic disease fluid protein 15 (GCDFP 15). The patient received adjuvant radiotherapy and is alive without any recurrence at 1 year of follow up. Apocrine adenocarcinomas are rare malignant skin adnexal tumors. Involvement of lacrimal sac is extremely rare with only one case reported in the literature till date. Immunohistochemistry utilizing GCDFP 15 stain can confirm the diagnosis.

Diagnostic circulating biomarkers to detect vision-threatening diabetic retinopathy: Potential screening tool of the future?

With the increasing prevalence of diabetes in developing and developed countries, the socio-economic burden of diabetic retinopathy (DR), the leading complication of diabetes, is growing. Diabetic retinopathy (DR) is currently one of the leading causes of blindness in working-age adults worldwide. Robust methodologies exist to detect and monitor DR; however, these rely on specialist imaging techniques and qualified practitioners. This makes detecting and monitoring DR expensive and time-consuming, which is particularly problematic in developing countries where many patients will be remote and have little contact with specialist medical centres. Diabetic retinopathy (DR) is largely asymptomatic until late in the pathology. Therefore, early identification and stratification of vision-threatening DR (VTDR) is highly desirable and will ameliorate the global impact of this disease. A simple, reliable and more cost-effective test would greatly assist in decreasing the burden of DR around the world. Here, we evaluate and review data on circulating protein biomarkers, which have been verified in the context of DR. We also discuss the challenges and developments necessary to translate these promising data into clinically useful assays, to detect VTDR, and their potential integration into simple point-of-care testing devices.

Clinical profile and management outcomes of lacrimal drainage system malignancies.

PURPOSE: To report the clinical profile and management outcomes of a series of cases of malignant tumors of the lacrimal drainage system (LDS). MATERIALS AND METHODS: A retrospective analysis of all cases diagnosed with LDS malignancy over the past 24 years (1995-2019) was done. Patient characteristics, tumor types, management, and outcomes were analyzed. RESULTS: A total of 14 patients were included. Thirteen cases were of primary malignancy, while one was a secondary lesion. The mean age was 42.5 years, with males and females being equally affected. A medial canthal mass was the most common (9, 64.2%) presentation. Six patients (42.8%) had undergone one or more dacryocystorhinostomy surgeries for nasolacrimal duct obstruction before presentation. Seven patients underwent wide local excision (50%) while 3 (21.4%) each underwent dacryocystectomy and exenteration. Adjuvant radiation was administered to 4 (28.5%) patients. Thirteen (92.8%) patients were diagnosed with epithelial malignancy while one (7.1%) was a case of small B cell lymphoma. Transitional cell carcinoma was the most common epithelial malignancy (4, 28.5%). Three (21.4%) patients had metastatic disease (2 lymph nodes and one angle of jaw). There was no mortality after a mean follow up of 40.7+_25.1 months (Median 26; Range 4-131). CONCLUSION: LDS malignancy is rare, with the epithelial variant being far more common than non-epithelial. Wide local excision with adjuvant radiotherapy is the preferred management. Long-term follow-up is essential to manage recurrences and to increase survival.

The spectrum and clinicopathological correlation of eyelid lesions: Twenty years' experience at a tertiary eye care center in South India.

PURPOSE: : To study the epidemiological pattern and diagnostic accuracy of histopathologically proven eyelid lesions over a period of two decades. METHODS: : A retrospective study of all histopathologically proven eyelid lesions from April 1996 to March 2016 was conducted. The lesions were broadly categorized as benign or malignant. Inflammatory and infectious lesions were included under the benign category. The percentage and diagnostic accuracy of each lesion was calculated. RESULTS: : There were a total of 994 (M = 551, F = 443) cases. The mean age of the patients was 43.5 ± 19.9 years. There were 809 (81.4%) benign and 185 (18.6%) malignant lesions. Benign lesions were commonly seen in the fourth decade, while the malignant ones in the late fifth decade. The upper lid was the most common site in both groups (n = 481, 48.4%). The commonest benign lesion was chalazion (n = 484, 59.8%). Dermal nevus (n = 94, 11.6%) was the most common benign neoplasm, while Molluscum contagiosum (n = 25, 3.09%) was the most common infectious lesion. Sebaceous gland carcinoma (SGC) (n = 103, 55.7%) was the leading malignant lesion followed by basal cell carcinoma (n = 39, 21.1%). Eleven malignant cases were misdiagnosed as benign (5.9%). Chalazion (99.1%) and SGC (65%) had the highest diagnostic accuracy, while Molluscum (40%) and squamous cell carcinoma (40%) were the most misdiagnosed lesions in the respective groups. CONCLUSION: : Benign eyelid lesions are far more common than malignant ones. Atypical and rare presentations may lead to misdiagnosis. Knowledge of epidemiological patterns and clinical features can help in achieving higher diagnostic accuracy.

Role of pre-operative percutaneous embolization in orbital alveolar soft part sarcoma - An experience from a tertiary eye-care center.

PURPOSE: To describe the clinic-radiological, pathological profile, and management outcomes of primary alveolar soft-part sarcoma (ASPS) of the orbit. METHODS: A retrospective analysis of all histopathologically proven cases of orbital ASPS that presented between May 2016 and September 2019 was done. Data collected included demographics, clinical features, imaging characteristics, metastatic workup, management, and follow-up. RESULTS: Five patients, of which four were males, presented to us during the study period. The mean age of presentation was 12.6 years (range 3-22 years). The most common presenting features were abaxial proptosis (n = 4) and diminished vision (n = 4). Imaging showed a well-defined orbital mass in all patients with internal flow voids in three. Preoperative percutaneous embolization with cyanoacrylate glue was done in these three patients owing to high vascularity. Four patients underwent complete tumor excision. One patient underwent exenteration. Histopathology showed polygonal tumor cells arranged in a pseudo-alveolar pattern and Periodic Acid-Schiff (PAS) positive crystals in the cytoplasm in all patients. One patient had systemic metastasis at presentation and developed a local recurrence after 3 months. No recurrence or metastasis was noted in the remaining four patients at a mean final follow-up of 11.2 months (range 5-15 months). CONCLUSION: ASPS is a rare orbital neoplasm that poses a diagnostic and therapeutic challenge. Imaging might show a soft-tissue tumor with high vascularity. Multidisciplinary management with interventional radiologists for preoperative embolization of vascular lesions helps minimize intraoperative bleeding and aids in complete tumor resection. A localized orbital disease carries a better prognosis.

Retinal Pigment Epithelium Adenoma and Adenocarcinoma: A Review.

Adenoma and adenocarcinoma of the retinal pigment epithelium (RPE) are rare intraocular tumours that are often misdiagnosed as posterior uveal melanoma or other simulating lesions. It is important to be able to differentiate these tumours from melanoma for 3 reasons. First, an inability to rule out melanoma often tilts the management towards enucleation. Second, management options like radiotherapy and local resection which work well for melanoma may not be easily applied to these tumours. Third, and most importantly, patients with melanoma need a lifetime follow-up to rule out metastases (metastatic dormancy) whereas RPE tumours hardly metastasize. An abruptly elevated, often deeply pigmented tumour, with a prominent retinal feeding artery and a draining vein causing exudation, should raise a suspicion of RPE tumours. RPE tumours have a remarkable local invasive potential but a low metastatic potential. Most RPE tumours require treatment due to local complications. Small, asymptomatic tumours can be generally observed. Enucleation is still the gold standard of treatment, although local resection has been reported in selected cases with good results. Here, we provide a comprehensive review of the demographic, clinical, and imaging features of true acquired neoplasms of the RPE, namely adenoma and adenocarcinoma, the ways to differentiate them from melanoma, their clinical course and prognosis, and Options for their management.

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.