Vaccination coverage against COVID-19 among rural population in Haryana, India: A cross-sectional study.

BACKGROUND: Conducting a study in rural pre-dominant areas will help to understand the penetration of the vaccination campaign during the COVID-19 health crisis. This study aimed to investigate vaccination coverage against COVID-19 among the rural adult population in India and to identify factors associated with vaccination coverage. METHODS: A population-based cross-sectional study was conducted among the rural population in one district of north India from January to February 2023. A semi-structured questionnaire was designed on the SurveyMonkey digital platform for interviewing the participants, which consisted of questions related to socio-demographic profile, health problems, vaccination status, types of vaccine, re-infection after vaccination, and functional difficulties. The data regarding infection with COVID-19 was collected based on self-reported positive testing for SARS-CoV 2 on RT-PCR. FINDINGS: A total of 3700 eligible individuals were enumerated for the survey, out of which 2954 (79.8%) were interviewed. The infection rate of past COVID-19 infection, based on self-report of testing positive, was 6.2% (95%CI: 5.3-7.1). Covishield vaccine was received by most participants (81.3%, 2380) followed by Covaxin (12.3%, 361) and Pfizer manufactured vaccine (0.03,1). The coverage for first, second, and booster doses of the vaccine was 98.2% (2902), 94.8% (2802), and 10.7% (315) respectively. The risk of reinfection at 12 months or more among participants with two doses of vaccine was 1.6% (46/2802, 95%CI: 1.2-2.1). The coverage among those with severe functional difficulties was lesser as compared to those with some or no difficulties. INTERPRETATION: Vaccination coverage against COVID-19 in rural Haryana, India is not dependent on factors like gender or occupation but is dependent on age and education. Although the full and partial vaccination coverage is high, the booster dose coverage is poor. In addition, the presence of severe disability was significantly associated with reduced vaccination coverage.

Identifying causes of vision loss and assistive technology needs among patients attending rehabilitation clinic of a tertiary care center in North India.

PURPOSE: Investigating the causes of visual loss and the best corrected visual acuity (BCVA) is crucial for identifying avoidable eye problems and planning appropriate rehabilitation and assistive technology (AT) services. The study aimed to identify various causes of vision loss and determine AT required for vision rehabilitation (VR). METHODS: The electronic records of patients who attended the VR clinic at a tertiary eyecare for the past 2 years were reviewed. Information such as demographics, BCVA, and causes of visual impairment were retrieved from the records. BCVA was categorized into better than or equal to 1/60 and less than <1/60 for AT services. RESULTS: In total, 1723 patients, mostly male (71.2%), visited the rehabilitation clinic from 2018 to 2019. Around 58.6% of patients belonged to the age group 16-49 years, whereas 25.6% were less than 15 years old. The most frequent eye problems were retinal disorders (63.5%), followed by retinitis pigmentosa (15.2%) and rod-cone dystrophy (4.7%). In contrast, congenital disorders were the most common cause of vision loss among younger groups. Approximately 36.0% of patients had <1/60 blindness and 16.6% had ≥1/60. Around 17.1% of patients would benefit from large prints (near vision acuity N18-N12). CONCLUSION: Early detection and timely management will prevent a significant proportion of patients from developing irreversible vision loss. Around one-third of patients would benefit from visual substitution AT.

Disinsert, retract and rotate technique of plaque brachytherapy.

BACKGROUND: Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed. PURPOSE: The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas. SYNOPSIS: The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration. HIGHLIGHTS: In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque. VIDEO LINK: https://youtu.be/YMIg3rYyp2o.

Axillary Lymph Node in Extra-Ocular Retinoblastoma - Benign or Malignant?

A 1-year-old male child presented with whitish discoloration of pupil of the left eye and swelling over the left axilla. A contrast-enhanced magnetic resonance imaging of the brain and orbits performed revealed left eye extra-ocular retinoblastoma. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan was done in this child as a part of baseline staging of retinoblastoma in an ongoing research project. The scan revealed left eye extra-ocular retinoblastoma along with calcified left axillary level I lymph node.

Tear Tacrolimus Levels and Clinical Response After Adjunct Therapy With Cutaneous Application of Tacrolimus 0.1% Over Upper Eyelid Skin in Chronic Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to evaluate the role of cutaneous application of 0.1% tacrolimus eye ointment over the skin of the upper eyelid in chronic vernal keratoconjunctivitis (VKC). METHODS: A prospective, longitudinal, noncomparative, open-label clinical study of moderate-to-severe grade steroid-dependent VKC was performed. Study participants were initiated on adjunct therapy of cutaneous application of 0.1% tacrolimus ointment twice daily on the upper eyelid skin. Ocular surface evaluation parameters, meibomian gland imaging, intraocular pressure, visual acuity, and clinical disease severity scoring were performed to assess clinical response at baseline and month 3 of therapy. Tear levels of tacrolimus were measured at month 3 using high-performance liquid chromatography tandem mass spectrometry and correlated with the clinical score. RESULTS: Palpebral form of VKC was observed in 85% of the cases, with positive family history in 5%, atopy in 7.5%, and keratoconus in 11.25%. Clinical assessment revealed improvement in 97.5% patients with discontinuation of concomitant topical steroids in 64% of patients. There were no changes in visual acuity, intraocular pressure, or ocular surface evaluation after therapy. Tacrolimus was detected in the tears of all our study patients after cutaneous application over the upper eyelid skin, proving its bioavailability with mean tear tacrolimus levels of 6.55 ± 21.43 ng/mL. Correlation analysis revealed a moderate negative correlation between the clinical score and tacrolimus concentration (Spearman correlation coefficient: -0.34, P = 0.002). CONCLUSIONS: Cutaneous tacrolimus 0.1% ointment over the upper eyelid skin is an efficacious alternative method of application in treatment of VKC, with no resultant ocular irritation.

Can Enhancement Pattern in Normal-Sized Optic Nerves on Magnetic Resonance Imaging Better Predict Tumor Invasion in Retinoblastoma Eyes?

Introduction: Optic nerve (ON) enhancement alone without ON thickening on contrast-enhanced magnetic resonance imaging (CE-MRI) can be associated with post-laminar optic nerve invasion (PLONI) in eyes with group E retinoblastoma. A few case reports and retrospective studies in the literature show a poor correlation between ON enhancement on MRI and ON invasion on histopathological examination (HPE). There is no universal consensus on the management of such cases. It is desirable that the presence and extent of a true ON invasion be reliably picked up before planning upfront enucleation in order to avoid stage II disease. Methods: In a prospective study conducted at a tertiary eye care center in North India, all retinoblastoma patients presenting with ON enhancement on imaging were evaluated. Demographic and imaging details, histopathological findings, and treatment details were recorded. The length and pattern of enhancement noted on MRI were correlated with histopathology. Follow-up was done till the end of the study period. Results: Six group E retinoblastoma eyes were evaluated. 3 eyes (50%) showed solid enhancement, 2 eyes (33.33%) had tram track pattern and 1 eye (16.66%) showed punctate enhancement pattern on CE-MRI. On histopathology, 5 (83.33%) cases showed PLONI and all 6 (100%) had ON head infiltration. The cut end of the ON was free in all cases. On correlating MRI and HPE, all eyes with solid enhancement pattern showed PLONI, of which 2/3 (66.6%) had diffuse ON infiltration. Only 50% of eyes with tram track patterns showed PLONI. The case which showed a punctate enhancement pattern showed focal infiltration by tumor cells with vacuolated cytoplasm on HPE. At the last follow-up, all patients were alive and free of disease. Conclusion: ON enhancement patterns may make it more predictive for PLONI on HPE. Solid enhancement pattern appears to correlate better with the extent of ON invasion on HPE, and longer lengths of solid ON enhancement may be considered for neoadjuvant chemotherapy rather than upfront enucleation.

Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma.

BACKGROUND: Pigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM. METHODS: Transmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers. RESULTS: Premelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression. CONCLUSION: Our results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.

Baseline and Post-NACT Imaging in Retinoblastoma With Optic Nerve Involvement: Can MRI Predict Prognosis?

PURPOSE: To describe a staging system for optic nerve invasion using magnetic resonance imaging (MRI) and report any correlation with survival outcome. METHODS: This was a ambispective study. Twenty-one patients with retinoblastoma who had optic nerve involvement on MRI were staged at baseline based on contrast enhancement and/or thickening and length of involvement. Response to neoadjuvant chemotherapy (NACT) was noted according to proposed response evaluation criteria and results were correlated with survival outcome. RESULTS: Baseline MRI staging was able to predict event-free survival (EFS) (P = .0015) using the log-rank test for trends. Patients with optic nerve enhancement alone showed 100% survival prognosis. Optic nerve thickening cases with complete or partial response to NACT showed better EFS (P > .90) than those with stable disease according to response evaluation criteria. CONCLUSIONS: The modified staging system for optic nerve invasion used in the current study significantly predicted EFS. The study also showed that response to NACT may be affected by baseline staging. The authors recommend that cases with optic nerve enhancement only, irrespective of the length of involvement (stage 0), may be treated with upfront enucleation. Cases with optic nerve thickening may be staged to evaluate the correlation with survival outcome in a larger cohort in future studies. [J Pediatr Ophthalmol Strabismus. 20XX;XX(X):XX-XX.].

Gamma Knife Radiosurgery for Uveal Melanoma: Our Experience and Thematic Review.

Background: Various therapies ranging from plaque brachytherapy to enucleation have been applied in uveal melanomas (UM). A gamma knife (GK) is the gold standard modality for head and neck radiation therapy with enhanced precision owing to the paucity of moving parts. The literature on GK usage in UM is rich with the methodology and nuances of GK applications undergoing constant change. Objectives: This article reports on the authors' experience in using GK for tackling UM followed by a thematic review of the evolution of GK therapy for UM. Materials and Methods: Clinical and radiological data of patients with UM treated with GK at the All India Institute of Medical Sciences, New Delhi, from March 2019 to August 2020 was analyzed. A systematic search for comparative studies and case series evaluating GK usage in UM was performed. Results: Seven UM patients underwent GK, with the median dose being 28 Gy at 50%. All patients underwent clinical follow-up and 3 patients had a radiological follow-up. Six (85.7%) eyes were preserved at follow-up, and 1 (14.28%) patient developed radiation-induced cataract. There was a reduction in tumor volume in all patients with radiological follow-up with the minimum being a 33.06% reduction in size compared to the presenting volume and the maximum being the complete disappearance of tumor at follow-up. A total of 36 articles presenting various facets of GK usage in UM have been thematically reviewed. Conclusion: GK can be a viable and effective eye-preserving option for UM with catastrophic side effects becoming rare owing to progressive reduction in radiation dose.

Implications of LAG3 and CTLA4 immune checkpoints beyond PD-1/PD-L1 as a potential target in determining the prognosis of uveal melanoma patients.

BackgroundResponse rate of PD-1/PD-L1 immunotherapeutic blockade agents in uveal melanoma (UM) is poor. Lymphocyte activation gene 3 (LAG3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are the two promising immune checkpoint targets. Therefore, our aim was to explore at how these proteins were expressed in tumour tissue and serum, as well as their prognostic implications in UM. METHODS: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was determined by immunohistochemistry in 54 enucleated UM tissue samples. mRNA expression level of LAG3 and CTLA-4 was determined by quantitative real-time PCR and corroborated by western blotting. Furthermore, soluble form of LAG3, CTLA-4 and CCR8 expression in serum was measured in 40 UM patients using ELISA. RESULT: The expression of LAG3, CTLA-4, CD3, CD4, CD8 and FOXP3 was observed in 30%, 33%, 41%, 35%, 50% and 39% of the cases, respectively. Loss of nBAP1 expression was significantly correlated with CD8+expression (p=0.012) but not with tumour infiltrating lymphocytes. LAG3 and CTLA-4 mRNA levels were higher in UM compared with normal uveal tissues. Higher LAG3 expression with CD8+expression was associated with lower metastasis-free survival (MFS) (p=0.049), but not with CTLA-4 in UM patients. MFS rate was reduced in patients having lower levels of CCR8 protein (p=0.050) and increased level of LAG3 protein (p=0.001). CONCLUSION: Our findings suggest that higher levels of LAG3 in UM with histopathologically high-risk parameters predict high metastatic potential and that it could be used as a targeted immunotherapy alone or in combination with PD-1/PD-L1 blockade agents.

Evaluation of liposomal amphotericin B for the treatment of fungal keratitis in a tertiary eye care hospital.

Purpose: To evaluate the efficacy of liposomal amphotericin B (L-AMB) for the treatment of fungal keratitis. Methods: Patients with fungal keratitis confirmed by potassium hydroxide (KOH) smear and/or confocal microscopy were administered topical L-AMB and randomized into three groups treated with three different formulations. The medication was administered two hourly till clinical improvement was achieved, followed by six hourly till complete resolution. The outcome measures were time to clinical improvement, resolution of epithelial defect, stromal infiltrate, hypopyon, extent and density of corneal opacity, neovascularization, and best corrected visual acuity (BCVA) at 3 months. Results: Mean age of the patients was 46.6 ± 14.8 years, and trauma with vegetative matter was the most common predisposing factor. Aspergillus flavus (36%) was the most common fungus cultured, followed by Fusarium (23%). Mean time to clinical improvement, time to resolution of epithelial defect, mean time to resolution of infiltrate, and time to resolution of hypopyon were 3.45 ± 1.38, 25.35 ± 8.46, 37.97 ± 9.94, and 13.33 ± 4.90 days, respectively, and they were comparable among the three groups. There was a significant difference between treatment failure and success cases in terms of days of presentation (P < 0.01), size of the epithelial defect (P-value 0.04), and infiltrate size at presentation (P-value 0.04). At 3 months follow-up, no statistically significant difference was noted in BCVA and mean scar size among groups. Conclusion: L-AMB in a gel form is an effective antifungal agent that promotes the healing of fungal ulcers with notably least vascularization and better tolerance. Trial registration number: CTRI/2020/04/024550.

Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients.

Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (p < 0.05). On Kaplan-Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.

Ocular surface characteristics in pediatric vernal keratoconjunctivitis: a clinico-cytological study.

PURPOSE: To compare the ocular surface parameters of children with vernal keratoconjunctivitis (VKC) with those of healthy controls and to correlate cytological characteristics with clinical findings and disease severity. METHODS: Newly diagnosed cases of VKC, not currently being treated, were recruited, along with age-matched controls with no ocular comorbidities. The Ocular Surface Disease Index questionnaire (OSDI) was administered to all children. Slit lamp biomicroscopy for meibomian gland dysfunction and ocular surface analysis was performed, including tear meniscus height, noninvasive tear film break-up time, lipid layer thickness, meibomian gland morphology, and meibomian gland duct distortion on meibography imaging. Conjunctival impression cytology was also performed. RESULTS: A total of 68 VKC patients and 33 controls were included. Statistically significant difference was seen in the mean OSDI score (30 ± 13.7 vs 16.1 ± 3 [P ≤ 0.01]), lipid layer thickness (24.2 ± 7.9 nm vs 69.9 ± 15.1 nm [P <0.001]), and noninvasive tear film break-up time (6.8 ± 1.7 vs 12.5 ± 1.8 sec [P < 0.01]) between groups. Mean tear meniscus height was 0.22 ± 0.06 mm in the VKC and 0.24 ± 0.04 mm in the control group (P = 0.096). Significant association was seen between grade of squamous metaplasia and severity of VKC (P < 0.01). Severity of VKC was found to be positively correlated with OSDI score (r = 0.767), grade of squamous metaplasia (r = 0.64) and negatively correlated with noninvasive tear film break-up time (r = -0.468), and lipid layer thickness (r = -0.253). CONCLUSIONS: This study highlights the poor ocular surface health of children with VKC, with severe disease being associated with worse forms of dry eye disease.

Recent Perspectives in the Management of Fungal Keratitis.

Mycotic keratitis is common in warm, humid regions with a varying profile of pathogenic fungi according to geographical origin, socioeconomic status, and climatic condition. Clinical diagnosis can be challenging in difficult cases and those refractory to treatment. Fungal hyphae on microscopic examination and culture isolation have been the gold standard in the laboratory diagnosis of fungal keratitis. A culture isolate of the aetiological fungus is essential to perform antifungal susceptibility testing. As the culture isolation of fungi is time-consuming, causing delays in the initiation of treatment, newer investigative modalities such as in vivo confocal microscopy and molecular diagnostic methods have recently gained popularity. Molecular diagnostic techniques now help to obtain a rapid diagnosis of fungal keratitis. Genomic approaches are based on detecting amplicons of ribosomal RNA genes, with internal transcribed spacers being increasingly adopted. Metagenomic deep sequencing allows for rapid and accurate diagnosis without the need to wait for the fungus to grow. This is also helpful in identifying new emerging strains of fungi causing mycotic keratitis. A custom-tear proteomic approach will probably play an important diagnostic role in future in the management of mycotic keratitis. Positive repeat cultures are being suggested as an important gauge indicative of a poor prognosis. Positive repeat fungal cultures help to modify a treatment regimen by increasing its frequency, providing the addition of another topical and oral antifungal agent along with close follow-up for perforation and identifying need for early therapeutic keratoplasty. The role of collagen crosslinking in the treatment of fungal keratitis is not convincingly established. Rapid detection by multiplex PCR and antifungal susceptibility testing of the pathogenic fungi, adopted into a routine management protocol of fungal keratitis, will help to improve treatment outcome. Early therapy is essential in minimizing damage to the corneal tissue, thereby providing a better outcome. The role of conventional therapy with polyenes, systemic and targeted therapy of antifungal agents, newer azoles and echinocandins in fungal keratitis has been widely studied in recent times. Combination therapy can be more efficacious in comparison to monotherapy. Given the diversity of fungal aetiology, the emergence of new corneal pathogenic fungi with varying drug susceptibilities, increasing the drug resistance to antifungal agents in some genera and species, it is perhaps time to adopt recent molecular methods for precise identification and incorporate antifungal susceptibility testing as a routine.

Intralenticular metallic foreign body 'locked-in' the posterior capsule and the utility of multimodal imaging.

Intraocular foreign bodies (FBs) are common ocular injuries reporting to the emergency services all over the world. The authors highlight the findings and surgical management of a case of intralenticular metallic FB following an injury while using chisel and hammer. The ocular path of the FB (2 mm) could be traced from a self-sealed corneal perforation, extending through the anterior capsule rupture, terminating at the posterior capsule, forming a posterior capsule tent with a part embedded in clear lens. Preoperative ultrasound biomicroscopy gave clues on posterior capsule integrity and the exact site of FB, and helped prognosticate and plan the surgical management of the case. The 'locked-in' FB was extracted after clear lens aspiration and posterior capsulorrhexis. The posterior capsule acted as a natural barrier between anterior and posterior segment, where the FB was found embedded.

Comparison of peribulbar block and subtenon infiltration in pediatric enucleation for retinoblastoma.

Purpose: Enucleation performed in children with retinoblastoma is associated with severe postoperative pain. The use of opioids for the pain is associated with numerous complications which demand careful monitoring. Subtenon infiltration and peribulbar block are useful in ameliorating pain perioperatively following various ophthalmic surgeries which are yet to be evaluated in enucleation. Therefore, we designed this study to compare the effects of peribulbar block and subtenon infiltration on postoperative pain with opioids in pediatric enucleation surgeries. Methods: 60 children of American Society of Anesthesiologists grade I and II, age ranging from 6 months to 6 years with retinoblastoma undergoing enucleation surgery were included in the study. Group A (n = 20): received peribulbar block (peribulbar group); Group B (n = 20): received subtenon local infiltration (subtenon group); and Group C (n = 20): no block was given. Results: The postoperative fentanyl consumption was lowest with Group B compared to Group A and Group C (P value 0.001). However, the total fentanyl consumption was comparable between groups A and B, while it was significantly higher in the control group. The mean pain score face, legs, activity, cry, consolability (FLACC) scale and mean time to discharge from post anesthesia care unit were lowest in Group B followed by Group A, while Group C had the highest. There was no statistically significant difference among the 3 groups with regards to side effects. Conclusion: Subtenon infiltration showed significantly better outcomes when compared to peribulbar block and intravenous opioids alone without any untoward adverse effects.

Peripheral ulcerative keratitis.

Peripheral ulcerative keratitis (PUK) is an inflammatory condition of the peripheral cornea with hallmark features of epithelial defects and stromal destruction as a result of a complex interplay of factors including host autoimmunity and the peculiar anatomic and physiologic features of the peripheral cornea and environmental factors. PUK may be the result of local or systemic causes and infectious or noninfectious causes. Arriving at a specific etiological diagnosis requires a meticulous clinical workup that may include a battery of laboratory and radiological investigations. Management by a team of internists or rheumatologists and ophthalmologists and judicious use of immunosuppressive agents may yield favorable results minimizing adverse effects. We review current clinical knowledge on the diagnosis and management of PUK.

Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters.

BACKGROUND: To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients. MATERIALS AND METHODS: Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines. RESULTS: Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ. CONCLUSION: Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.

Combined association of massive choroidal and optic nerve invasion as a prognostic relevance in primary retinoblastoma: A 10-year study.

PURPOSE: To determine the significance of both massive choroidal invasion and optic nerve invasion (retrolaminar [(RL]+cut end [CE]) as a criterion for classifying high metastatic potential retinoblastoma and their relationship with other known histopathological high-risk features. METHODS: A retrospective review of 650 eyes diagnosed as retinoblastoma over a 10-year period. In our study, there is male predominance and a higher percentage of the poorly differentiated tumors. The age of most of the patients ranges from 1 month to 8 years with a median age of 2 years. RESULTS: There were 24% of eyes with massive choroidal invasion and 18% of eyes with optic nerve invasion up to the cut end. On performing Cox-proportional hazard analysis, it was found that massive choroidal invasion in association with optic nerve invasion up to the cut end was an independent prognostic parameter. On Kaplan-Meier analysis, overall survival had reduced in patients having both massive choroidal invasion and an optic nerve cut end invasion along with orbital invasion (P < .05). CONCLUSION: The presence of massive choroidal invasion in association with optic nerve cut end invasion (RL+CE) could be used as a better prognostic predictor in assessing retinoblastoma patients with high metastatic potential and need to be kept for longer follow up.