The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

Purpose: To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. Methods: Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. Results: The mean age at diagnosis was 17 years (range 5.0-24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). Conclusions: We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

Evaluation and management of a spontaneous corneal rupture secondary to pellucid marginal degeneration, using swept-source anterior segment optical coherence tomography.

We describe a case of bilateral spontaneous corneal perforation secondary to pellucid marginal degeneration and present the associated swept-source anterior segment optical coherence tomography (SS-ASOCT) findings and management principles used. A 47-year-old woman presented with ocular pain, redness, foreign body sensation and clear discharge in the right eye in 2017 and with very similar symptoms in 2019 in the left eye. Clinically she had a corneal perforation at the inferior cornea with associated loss of anterior chamber volume. Corneal topography demonstrated peripheral thinning and steepening in the contralateral eye. ASOCT images revealed full-thickness perforation, iridocorneal touch and iris stranding. The patient was managed with a combination of contact bandaging and corneal gluing. SS-ASOCT is a useful adjunctive tool in the clinical assessment and evaluation of spontaneous corneal perforation. Alongside the clinical evaluation, it can be used to monitor the clinical response.

Ultra-wide-field imaging assessment of small choroidal pigmented lesions using red and green colour channels.

BACKGROUND: Diagnosis of small choroidal melanoma is mainly based on tumour thickness, subretinal fluid, or lipofuscin pigment. Ultra-wide-field imaging (UWF) allows depiction of choroidal lesions through a red (RC) and a green channel (GC). Aim of the study was to determine the utility of this tool in the detection of small choroidal melanoma. METHODS: Retrospective cross-sectional study of patients with small choroidal pigmented lesions up to 3 mm in thickness. All patients underwent clinical and imaging assessment including UWF. Lesions were subcategorized based on thickness and lesion type. A qualitative assessment ensued using the red and green channels feature. RESULTS: A total of 152 patients were included. Melanotic naevi (76/152,50%) and small choroidal melanomas (55/152,36%) were the predominant types. Thickness was <1 mm in 30% (46/152), 1-2 mm in 46% (70/152) and 2-3 mm in 24% (36/152) of cases. Two distinct imaging patterns were noted: dark on RC/undetectable on GC and dark on RC/light on GC. In melanotic naevi the dark on RC/light on GC pattern was significantly associated with increased tumour thickness (p = 0.006) and the presence of lipofuscin (p < 0.001) suggesting a potential prognostic significance. In small melanomas such an association was not established. The majority of small melanomas manifested a dark on RC/undetectable on GC pattern despite the presence of subretinal fluid and lipofuscin. CONCLUSIONS: UWF imaging of choroidal pigmented tumours with red-green channels revealed two distinct patterns. The dark on RC/light on GC pattern was more common in suspicious melanotic naevi, but not in small melanomas. The use of red-green channels is not a reliable diagnostic tool in the early detection of small melanomas.

Eye clinic liaison officers service in the United Kingdom.

BACKGROUND: To investigate the role of eye clinic liaison officers (ECLOs) in the United Kingdom and analyse patients' demographics and services provided. METHODS: This is a retrospective observational study. Data were collected from the Royal National Institute of Blind People for ECLOs in Wales, Scotland, Northern Ireland and England for the first quarter of 2015. Statistical analysis was performed using chi-square and t test as appropriate. RESULTS: Trusts with ECLOs support vary greatly in the UK regions. Only one-third of NHS trusts in England have an ECLO service. Over 4000 patients were assessed. The majority of patients were of White ethnic background (94%), lived alone (37%), had no carers (58%) and were in their 80s (29.5%). The principal ocular conditions causing sight loss and certification were age-related macular degeneration (41.6%) and glaucoma (18.1%). Approximately 70% of patients are first seen at 13 to 18 months from diagnosis. CONCLUSIONS: ECLO services vary in the UK regions. England has the lowest ECLO availability per trust and the majority of those assessed were of White British origin with AMD. There are significant delays from diagnosis to the first visit indicating the need for improved services. Further studies are necessary to develop the evidence base for the expansion and funding of ECLO services.

Worldwide inequality in access to full text scientific articles: the example of ophthalmology.

BACKGROUND: The problem of access to medical information, particularly in low-income countries, has been under discussion for many years. Although a number of developments have occurred in the last decade (e.g., the open access (OA) movement and the website Sci-Hub), everyone agrees that these difficulties still persist very widely, mainly due to the fact that paywalls still limit access to approximately 75% of scholarly documents. In this study, we compare the accessibility of recent full text articles in the field of ophthalmology in 27 established institutions located worldwide. METHODS: A total of 200 references from articles were retrieved using the PubMed database. Each article was individually checked for OA. Full texts of non-OA (i.e., "paywalled articles") were examined to determine whether they were available using institutional and Hinari access in each institution studied, using "alternative ways" (i.e., PubMed Central, ResearchGate, Google Scholar, and Online Reprint Request), and using the website Sci-Hub. RESULTS: The number of full texts of "paywalled articles" available using institutional and Hinari access showed strong heterogeneity, scattered between 0% full texts to 94.8% (mean = 46.8%; SD = 31.5; median = 51.3%). We found that complementary use of "alternative ways" and Sci-Hub leads to 95.5% of full text "paywalled articles," and also divides by 14 the average extra costs needed to obtain all full texts on publishers' websites using pay-per-view. CONCLUSIONS: The scant number of available full text "paywalled articles" in most institutions studied encourages researchers in the field of ophthalmology to use Sci-Hub to search for scientific information. The scientific community and decision-makers must unite and strengthen their efforts to find solutions to improve access to scientific literature worldwide and avoid an implosion of the scientific publishing model. This study is not an endorsement for using Sci-Hub. The authors, their institutions, and publishers accept no responsibility on behalf of readers.

Swept-Source OCT and Near-Infrared Reflectance Patterns in Choroidal Nevi.

PURPOSE: To describe the 3 distinct patterns of choroidal nevi in swept-source (SS) OCT and apply that classification to a cohort of consecutive choroidal nevi. Also, we aim to describe the findings of these lesions in near-infrared reflectance (NIR) at different wavelengths (820 and 1050 nm). DESIGN: Single-center, retrospective, observational study. PARTICIPANTS: One hundred four consecutive patients with choroidal nevi. METHODS: Retrospective analysis of choroidal nevi imaged with SS OCT and NIR. MAIN OUTCOME MEASURES: Lesions were classified according to OCT patterns as type A (high reflectivity with optical shadowing), type B (medium reflectivity with partial visualization of the scleral boundary), and type C (hyporeflective with complete visualization of the scleral boundary). RESULTS: Of 104 choroidal nevi, 97 lesions (93.3%) could be classified into 1 of the SS OCT patterns. Forty-nine percent corresponded to type A, 26% corresponded to type C, and 18.3% corresponded to type B. In NIR (n = 820), 76% of lesions were hyperreflective, whereas in NIR (n = 1050), most of the lesions were hyporeflective (59.6%; inverse reflectance). CONCLUSIONS: Choroidal nevi present distinct patterns according to SS OCT features. Clinical implications are yet to be determined. In NIR, inverse reflectance may be a consequence of the confocality of the device, rather than a property of the lesions.

Microperimetry and swept-source optical coherence tomography in the assessment of the preferred retinal locus in a child with macular retinoblastoma in the remaining eye.

Assessing the visual capabilities that remain to children affected with bilateral retinoblastoma has relied on psychophysical tests based on recognition visual acuity. We report a case in which fundus-driven perimetry and swept-source optical coherence tomography was performed in a patient with a macular tumor in the remaining eye as a novel way of further assessing fixation after oncological disease and treatment.

Detection of extrascleral extension in uveal melanoma with histopathological correlation.

PURPOSE: Uveal melanoma is the most common primary intraocular malignancy. Extrascleral extension (ESE) is rare, but associated with an increased rate of orbital recurrence and an overall poor prognosis. Clinical studies show low rates when compared with histological studies. Due to the prognostic importance of ESE, we sought to compare our clinical, intraoperative, and histological detection rates. DESIGN: A retrospective cross-sectional case series. METHODS: A list of eyes enucleated for uveal melanoma was compiled from the admissions records of the London Ocular Oncology Service during the 28-month period, i.e. January 2010-April 2012. The surgical and clinical notes of patients with histopathology proven ESE were reviewed to determine when it was first diagnosed or suspected. The subsequent management of these cases is discussed. RESULTS: A total of 16 out of 174 (9%) eyes had histologically proven ESE. Eight of 16 cases were detected preoperatively at clinical examination, including the use of ocular ultrasound, 3 of 16 were discovered intra-operatively, and 5 of 16 deemed microscopic ESE, were first detected on histological examination. Seven of 7 (100%) of cases with anterior ESE were detected clinically by slit lamp biomicroscopy, while only 1 out of 9 (11%) of cases with posterior ESE was detected preoperatively with ultrasound. CONCLUSIONS: Slit lamp biomicroscopy is sensitive for detecting anterior ESE. Most posterior ESE is microscopic, but macroscopic posterior ESE may also be missed by B-scan ocular ultrasound. Orbital surgeons should be suspicious of clinically undetected posterior ESE, and consider adjuvant orbital radiotherapy in cases with macroscopic ESE.

MULTIMODALITY IMAGING OF TORPEDO MACULOPATHY WITH SWEPT-SOURCE, EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Multimodality image analysis of two cases of torpedo maculopathy. METHODS: Imaging with fundus photography, autofluorescence (AF), swept-source optical coherence tomography (OCT), en face OCT, and OCT angiography. RESULTS: The basal diameter of the torpedo lesions was 1 mm × 2 mm. One case had a satellite lesion. Autofluorescence indicated variable loss of signal. Swept-source OCT and en face OCT demonstrated fundus excavation, attenuation of nuclear layers and disruption of the outer plexiform layer, loss of photoreceptors and a subretinal cleft. In one case, Sattler layer appeared extended at the cleft. Optical coherence tomography angiography indicated loss of flow in deep retinal vessels and increased flow in choroidal vessels surrounding the cleft. CONCLUSION: Multimodal imaging findings of torpedo maculopathy include disruption of the deep retinal capillary network, expansion of Sattler layer, and increased signal around the subretinal cleft.

Analysis of Long-term Outcomes of Radiotherapy and Verteporfin Photodynamic Therapy for Circumscribed Choroidal Hemangioma.

PURPOSE: To determine the long-term therapeutic outcome for different treatments of circumscribed choroidal hemangioma (CCH). DESIGN: Retrospective observational study. SUBJECTS: Patients with newly diagnosed CCH. METHODS: Observation, verteporfin (Visudyne) photodynamic therapy (PDT), lens-sparing external beam radiotherapy (LS-EBRT), or plaque brachytherapy. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at baseline and throughout follow-up, tumor dimensions, and OCT central thickness (where available) at baseline and throughout follow-up were recorded. RESULTS: There were 60 treatment-naïve consecutive cases with CCH between January 2000 and June 2014; 42 (70%) received treatment. These were LS-EBRT (23/60 [38%]; mean follow-up, 45.5 months), PDT (16/60 [27%]; mean follow-up, 38 months), and plaque radiotherapy (3/60 [5%]; mean follow-up, 92 months). Macular location, mottled or orange pigment, and absence of drusen were significantly more frequent in the treatment group. In the LS-EBRT group, median thickness reduction on ultrasound B scan was 1.6 mm (mean ± standard deviation, 1.65±1.6; range, -6.5 to +0.7). The mean ± standard deviation BCVA gain was 0.22±0.34, with >3 Snellen lines in 48% of cases. Kaplan-Meier estimates were 80% for any gain and 40% for >3 Snellen lines gain at 5 years. In the PDT group, the median decrease in thickness was 0.95 mm (mean ± standard deviation, 1.0±0.8; range, -2.5 to +0.2). The mean ± standard deviation BCVA gain was at 0.3±0.51, with >3 Snellen lines in 30% of cases. Kaplan-Meier estimates were 93% for any gain and 68% for >3 Snellen lines at 5 years. Double versus single duration PDT had more favorable outcomes with a greater reduction in tumor thickness (P = 0.04), central retinal thickness (P = 0.02), and improvement in visual acuity (median, 0.33 vs -0.05). There was no difference in decrease in tumor thickness or BCVA gain between the LS-EBRT and PDT groups. With plaque brachytherapy, the mean decrease in thickness was 2.5 mm, but BCVA loss of >2 Snellen lines was noted in all 3 cases at the end of follow-up. Radiation complications developed in 10 of 23 cases (43.5%) from the LS-EBRT group and 2 of 3 cases (67%) from the plaque brachytherapy group. CONCLUSIONS: LS-EBRT is equivalent to PDT in CCH management for post-treatment BCVA and tumor thickness reduction. The risk of LS-EBRT and plaque brachytherapy was late radiation-related complications. Double duration PDT was more favorable than single duration.

Multimodal Imaging Analysis in a Case with Congenital Fovea-Involving Retinal Macrovessel and Excellent Visual Acuity.

PURPOSE: Congenital retinal macrovessels (CRM) represent rare aberrant vasculature of the retinal vessels that can supply or drain the macula. In this report, the optical coherence tomography angiography features of a congenital retinal macrovessel are discussed. METHODS: The history and examination findings are presented alongside swept-source OCT angiography with corresponding B scan and en face OCT imaging. PATIENTS: The case is a 12-year-old female patient with excellent best-corrected visual acuity in both eyes. RESULTS: Swept-source OCT angiography demonstrated considerable loss of the foveal avascular zone at the levels of the superficial and deep capillary plexus. DISCUSSION: In this case there was no detrimental effect on vision despite anatomical loss of the foveal avascular zone.

Secondary Resistance to Vismodegib After Initial Successful Treatment of Extensive Recurrent Periocular Basal Cell Carcinoma with Orbital Invasion.

Vismodegib is proven to be effective in the treatment of locally advanced and metastatic basal cell carcinoma, but evidence of resistance is beginning to emerge. A case of advanced recurrent periocular basal cell carcinoma which responded dramatically to vismodegib after 3 months but recurred after 9 months due to drug resistance, eventually requiring orbital exenteration, is presented. The mechanism of vismodegib resistance is discussed.

Nonteratoid Medulloepithelioma Presenting in a 78-Year-Old Male.

BACKGROUND: Medulloepithelioma is a rare congenital neoplasm derived from precursors of the nonpigmented ciliary epithelium of the ciliary body. The average patient age at clinical presentation is 3.8 years. CASE PRESENTATION: We present the case of a 78-year-old male with progressive lens subluxation and ocular hypertension who was found to have a ciliary body mass. After enucleation for presumed ciliary body melanoma, histopathology showed a nonteratoid medulloepithelioma. Cytogenetic analysis revealed abnormalities in chromosomes 3 and 8. CONCLUSION: Medulloepithelioma is often initially misdiagnosed. Though congenital in nature, it can exhibit rapid growth, have chromosomal abnormalities, and must be considered in all age groups.

Atypical Presentation of Low-Grade Small Lymphocytic Lymphoma of the Lacrimal Sac.

Lymphoma of the lacrimal sac is uncommon and usually presents as a lacrimal sac mass, against a background of known systemic lymphoma. This study presents the case of a 70-year-old man with small lymphocytic lymphoma of the lacrimal sac and widespread systemic involvement presenting as common canalicular obstruction without a palpable mass or systemic symptoms.

Metabolic activity of primary uveal melanoma on PET/CT scan and its relationship with monosomy 3 and other prognostic factors.

PURPOSE: To correlate the metabolic activity of primary uveal melanoma on positron emission tomography (PET)/CT scan with known clinical and pathological prognostic factors. METHODS: A retrospective cohort analysis of eyes enucleated for uveal melanoma that underwent preoperative imaging with a PET/CT scan was performed. Tumour dimensions were recorded and classified using Collaborative Ocular Melanoma Study (COMS) and American Joint Committee on Cancer (AJCC) Tumour - Nodes - Metastases (TNM) criteria. Metabolic activity was determined by measurement of the maximal standardised uptake value (SUVmax) on PET/CT scans. SUVmax of >2.5 and >4 was also used as cut-off value for metabolic positivity. Chromosome 3 and 8 status was determined using fluorescence in situ hybridisation analysis. Pearson correlation, χ(2) test and non-parametric tests were used. p<0.05 was considered statistically significant. RESULTS: Seventy-six uveal melanomas were imaged preoperatively with a PET/CT scan. Overall 92% of tumours had a SUVmax >2.5 and 67% had a SUVmax >4. Monosomy 3 was found in 35 melanomas, of which 94% had an SUVmax >2.5 and 80% had an SUVmax >4. Only 57% of disomy 3 melanomas had an SUVmax >4. SUVmax was significantly increased in tumours with monosomy 3 (p=0.043) but not in tumours with chromosome 8 gain (p=0.49). SUVmax and increasing tumour size were positively correlated (p<0.05). Using the AJCC criteria, there was a significant difference in SUVmax among prognostic groups (p=0.024). There was no correlation with histopathological cell type (p=0.923). CONCLUSIONS: Metabolic activity of uveal melanoma on PET/CT scan is positively correlated with monosomy 3, increasing tumour size and TNM prognostic groups. No association with chromosome 8 gain or histopathology cell type was noted. SUVmax >4 is a relative but not an absolute indicator of monosomy 3 status.

Evaluation of retinal pigment epithelium-Bruch's membrane complex thickness in dry age-related macular degeneration using optical coherence tomography.

AIM: To compare retinal pigment epithelium-Bruch's membrane (RPE-BM) complex thickness in patients with early and intermediate dry age-related macular degeneration (AMD) and age-matched controls using spectral domain optical coherence tomography (SD-OCT). METHODS: In this retrospective, cross-sectional study, 25 patients with dry AMD and 25 controls were recruited. SD-OCT scans were manually segmented by two independent investigators. Thickness values were calculated for the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. RESULTS: RPE-BM thickness was significantly thicker in the dry AMD group (32.3, 30.6 and 28.4 µm for central, inner and outer subfields, respectively) compared with the normal eyes (22.7, 21.8 and 21.6 µm, respectively). RPE-BM thickness was positively correlated with age in the normal group but not in the AMD group. RPE-BM thickness in the dry AMD group was negatively correlated with visual acuity in the central and inner subfields but not in the outer. We observed good intraobserver and inter-observer reliability for both groups in all ETDRS subfields. CONCLUSIONS: This study reports novel data concerning RPE-BM segmentation in dry AMD and performs a direct comparison with age-matched normal controls. Our findings confirm the electron and light microscopy derived data and also establish the value of OCT in the quantification of the RPE-BM complex.

Choroidal naevi complicated by choroidal neovascular membrane and outer retinal tubulation.

AIMS: To present the outcomes of a series of patients with choroidal neovascular membrane (CNV) secondary to a choroidal naevus and report the presence of outer retinal tubulation. METHODS: In this retrospective series, patients underwent a complete clinical and imaging assessment (fundus photo, fluorescein angiography and optical coherence tomography) and were observed or managed with intravitreal anti-VEGF injections dependent on whether visual acuity was affected. RESULTS: Seventeen patients were included in this study. Of this, 46% (8/17) had classic or predominantly classic CNV and 53% (9/17) had occult or minimally classic CNV. Active treatment with intravitreal anti-VEGF injections was required in 35% (6/17). Visual acuity improved in three eyes by 2-4 Snellen lines, remained stable in one eye and worsened in two eyes by 2 Snellen lines. CNV partially regressed in five cases. In the observation group (65%, 11/17), visual acuity did not change during follow-up period. Outer retinal tubulation was found in 18% (3/17). CONCLUSIONS: Anti-VEGF treatment is effective in the management of vision threatening CNV secondary to a choroidal naevus. Functional or anatomical improvement was obtained in 66% of treated eyes. Outer retinal tubulation, noted in 18%, showed the clinical importance of this sign in determining continuation of anti-VEGF treatment.