Germline retinoblastoma: estimating risk and counselling the family

Even when a diagnosis of germline retinoblastoma cannot be confirmed by genetic testing, the risk to family can still be estimated and used to plan follow-up eye examinations

Is tumour thickness measurement required for MOLES scoring of melanocytic choroidal tumours?

Introduction: It can be challenging to distinguish between choroidal naevi and melanomas in the community setting, particularly without access to ultrasonography, required to measure the thickness of melanocytic choroidal tumours. We aimed to determine whether thickness measurement is required for MOLES scoring of melanocytic choroidal tumours. Methods: The dataset of a recent MOLES evaluation was reviewed. Patients were selected for the present study if their MOLES tumour size category was determined by tumour thickness measured with ultrasonography (US). The largest basal tumour diameter and tumour thickness were then measured from ultra-widefield fundus images and optical coherence tomography (OCT) images, respectively. Results: The tumour size category was determined by tumour diameter in 203/222 (91.4%) with no influence of tumour thickness. The tumour thickness influenced the MOLES score in 19/222 (8.6%) patients. In 11/19 patients with OCT measurements of tumour thickness, the US measurement exceeded the OCT by more than 25% in 5 patients, more than 50% in 2 patients and more than 75% in 1 patient. As a result, the revised tumour thickness based on OCT determined the size category in 4/216 (1.8%) patients. The Optos measurements increased the diameter score by 1 in 5 patients. As a result, the revised tumour thickness determined the size category in 4/216 (1.8%) patients. If both the revised diameter and thickness scores were considered, the MOLES score reduced in 4 patients. If both the diameter and thickness scores were considered, the MOLES score reduced in 5 and increased in 1. Only 0.94% (2/211) of melanocytic choroidal tumours assessed with MOLES when using Optos ultra-widefield fundus images diameter and OCT to measure tumour diameter and thickness, respectively, required a change in management from a reduction in MOLES score from 1 to 0. Discussion/Conclusion: This study suggests that the MOLES category for size is influenced more by the tumour diameter, if it can be measured accurately, than by the thickness. This study suggests ignoring tumour thickness if this cannot be measured accurately with OCT, unless the tumour has a mushroom shape

Genetic analysis of ocular tumour-associated genes using large genomic datasets: insights into selection constraints and variant representation in the population

Background: Large genomic databases enable genetic evaluation in terms of haploinsufficiency and prevalence of missense and synonymous variants. We explored these parameters in ocular tumour-associated genes.// Methods: A curated list of ocular tumour-associated genes was assessed using the genomic databases Genome Aggregation Database (gnomAD) and DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) and compared with breast and lung cancer-associated gene lists. Haploinsufficiency was determined based on specific criteria: probability of loss of function index ≥0.9 in gnomAD, upper CI O/E limit <0.35 for loss of function variants in gnomAD and/or a DECIPHER pHaplo ≥0.86. UniProt was used for further gene characterisation, and gene ontology Protein Analysis THrough Evolutionary Relationships was explored for common biological pathways. In addition, we identified genes with under-representation/over-representation of missense/synonymous variants.// Results: Fifty-seven genes were identified in association with ocular and extraocular tumours. Regarding haploinsufficiency, 41% of genes met the criteria for negative selection, with 57% categorised as tumour-suppressing and 39% as oncogenic. Most genes were involved in regulatory processes. Regarding triplosensitivity, 33% of genes reached significance and 83% of these were haploinsufficient. Analysis of variants revealed under-representation of missense variants in 23% of genes and over-representation of synonymous variants in 5% of genes. Ocular tumour-associated genes exhibited higher scores for haploinsufficiency and triplosensitivity compared with breast and lung cancer-associated genes. Pathway analysis revealed significant enrichment in cellular proliferation, differentiation and division. Encoded proteins of ocular tumour-associated genes were generally longer than the median of the UniProt database.// Conclusion: Our findings highlight the importance of negative selection in ocular tumour genes, supporting cranial gene conservation. This study provides insights into ocular tumourigenesis and future research avenues

Applications of three-dimensional printing in ophthalmology

Three-dimensional (3D) printing is increasingly used to produce customised objects and is a promising alternative to traditional manufacturing methods in diverse fields, such as dentistry and orthopaedics. Already in use in other medical specialities, adoption in ophthalmology has been limited to date. This review aims to provide an overview of 3D printing technology with respect to current and potential applications in ophthalmic practice. Medline, Embase and internet search were performed with "3D printing", "ophthalmology", "dentistry", "orthopaedics" and their synonyms used as main search terms. In addition, search terms related to clinical applications such as "surgery" and "implant" were employed. 3D printing has multiple applications in ophthalmology, including in diagnosis, surgery, prosthetics, medications and medical education. Within the past decade, researchers have produced 3D printed models of objects such as implants, prostheses, anatomical models and surgical simulators. Further development is necessary to generate optimal biomaterials for various applications, and the quality and long-term performance of 3D models needs to be validated

The Fate of RPE Cells Following hESC-RPE Patch Transplantation in Haemorrhagic Wet AMD: Pigmentation, Extension of Pigmentation, Thickness of Transplant, Assessment for Proliferation and Visual Function—A 5 Year-Follow Up

(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)—the patch—and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject

Ocular rhinosporidiosis mimicking conjunctival squamous papilloma in Kenya - a case report.

BACKGROUND: Ocular rhinosporidiosis is a chronic granulomatous infection caused by a newly classified organism that is neither a fungus nor bacterium. It often presents as a benign conjunctival tumour but may mimic other ocular conditions. It is most often described in India. In Africa cases have been reported from South Africa, Kenya, Tanzania, Malawi, Uganda, Congo and Ivory Coast. CASE PRESENTATION: A 54 year old man was seen in Kenya with a lesion that resembled a conjunctival papilloma. We report resemblance to conjunctival papilloma and the result of vital staining with 0.05% Toluidine Blue. CONCLUSION: Ocular rhinosporidiosis occurs in East Africa. It may resemble conjunctival squamous papilloma. Vital staining with 0.05% Toluidine blue dye did not distinguish the two lesions well

Systemic adjuvant chemotherapy for advanced malignant ocular medulloepithelioma

BACKGROUND: Ocular medulloepithelioma (diktyoma) is a rare and potentially malignant paediatric tumour of the non-pigmented ciliary epithelium. Adjuvant chemotherapy can be given in advanced cases, but the indications and regimens remain to be defined. The aim was to identify whether adjuvant chemotherapy offers treatment benefit in advanced ocular medulloepithelioma. METHODS: This was a retrospective case series of subjects referred to a single specialist ocular oncology centre for advanced ocular medulloepithelioma subsequently treated with enucleation, including those needing adjuvant systemic vincristine, etoposide and carboplatin. A case-note review was performed for included subjects meeting referral criteria. The outcomes were histopathology characteristics, recurrence, metastases and survival. RESULTS: Between March 2010 and June 2017, four male patients (mean age 31 months) underwent enucleation for ocular medulloepithelioma. Adjuvant chemotherapy was commenced in 3 patients (75%) due to malignant histopathological features. With a mean follow-up time of 81.5 months (median 71 months, range 49-135 months) none of the patients have had recurrence, metastases or death from the tumour. CONCLUSIONS: This series is unique in reporting the management of advanced malignant ocular medulloepithelioma with adjuvant systemic vincristine, etoposide and carboplatin for advanced tumours with malignant features. This regimen appears to be safe and may be effective in preventing metastatic spread