Posterior vitreous membrane findings on OCT related to collagen type IV abnormalities.

INTRODUCTION: The pathological mechanisms of abnormal collagen type IV predisposing to macular hole formation in Alport syndrome are hypothesized to be related to defective Bruch's membrane leading to ruptured intraretinal cysts. However, abnormal collagen type IV may also predispose to macular hole formation due to vitreous cortex abnormalities. METHODS: An observational case series of Optical Coherence Tomography (OCT) findings in three patients. RESULTS: In two patients diagnosed with Alport syndrome and in one patient with a possibly pathogenic genetic variant in COL4A3 we observed a remarkable posterior vitreous cortex with a vitreoschisis-like appearance on OCT. Two of these patients developed a rhegmatogenous retinal detachment, of which one was caused by a giant retinal tear, and one patient developed a macular hole. During surgery, a firmly adherent vitreous cortex was observed centrally in the left eye and in the midperiphery in the right eye in one patient with a macular hole and giant retinal tear, respectively. CONCLUSION: These new vitreous cortex findings in patients with Alport syndrome are possibly related to pathogenic genetic variants affecting type IV collagen. Abnormal type IV collagen may cause pathological vitreoretinal traction, potentially leading to an increased risk of macular holes and rhegmatogenous retinal detachments.

The genetics and disease mechanisms of rhegmatogenous retinal detachment.

Rhegmatogenous retinal detachment (RRD) is a sight threatening condition that warrants immediate surgical intervention. To date, 29 genes have been associated with monogenic disorders involving RRD. In addition, RRD can occur as a multifactorial disease through a combined effect of multiple genetic variants and non-genetic risk factors. In this review, we provide a comprehensive overview of the spectrum of hereditary disorders involving RRD. We discuss genotype-phenotype correlations of these monogenic disorders, and describe genetic variants associated with RRD through multifactorial inheritance. Furthermore, we evaluate our current understanding of the molecular disease mechanisms of RRD-associated genetic variants on collagen proteins, proteoglycan versican, and the TGF-ß pathway. Finally, we review the role of genetics in patient management and prevention of RRD. We provide recommendations for genetic testing and prophylaxis of at-risk patients, and hypothesize on novel therapeutic approaches beyond surgical intervention.

Risk factors and management of primary giant retinal tears.

PURPOSE: To describe clinical characteristics and management in a large cohort of patients with retinal detachment due to a giant retinal tear (GRT). METHODS: We performed a retrospective cohort study with 222 eyes of 206 patients with a primary and non-traumatic GRTs between 2005 and 2022. We analysed the relevant clinical and surgical data from these patients. RESULTS: Eighty-six per cent (n = 177) of patients were male. We observed no relation between refractive error and GRT size (Spearman's rho: r = -0.018, p = 0.83). We achieved a primary and final treatment success in 77%, respectively 92%, of eyes. The final visual outcome was 20/40 or better in 65% and 36% of eyes in fovea-on and fovea-off GRTs respectively. Thirty-five per cent (n = 73) of patients developed a retinal detachment in the fellow eye. The median time until a retinal detachment in the fellow eye occurred after GRT was 20 months, and 10% developed within 1 month. A prediction model for the development of retinal detachment in the fellow eye resulted in a receiver operating characteristics curve with an area under the curve of 0.68 (95% CI: 0.57-0.78, p = 0.001). CONCLUSION: We observed a highly significant gender imbalance in patients with a non-traumatic GRT. One third of patients developed a retinal detachment bilaterally. Ten per cent of fellow eye's retinal detachment that develop after GRT, occur within 1 month. Clinical parameters showed limited predictive value for a retinal detachment in the fellow eye. These findings suggest an underlying genetic factor.

Air versus fluorinated gas tamponades in pars plana vitrectomy treatment for primary rhegmatogenous retinal detachment.

PURPOSE: To compare the treatment success of air with fluorinated gas (20% SF6 or 14% C3 F8 ) tamponade in pars plana vitrectomy for primary rhegmatogenous retinal detachment. METHODS: A retrospective cohort study comprised of 1023 consecutive primary retinal detachment cases between 2014 and 2020. We employed a univariate multivariable binary logistic regression model. RESULTS: We used intraocular gas tamponades in 872 cases with PVR grade B or lower: air tamponade was used in 414 eyes and 458 eyes were treated with a type of fluorinated gas tamponade. There was no significant difference in the type of tamponade with regard to the re-detachment rate (95% CI -1.0% and 4.1%). Additionally, also in the subgroup of rhegmatogenous retinal detachments with inferior located retinal defects we found no significant difference between the two types of tamponade (p = 0.54 Fisher's exact). The multivariable model, which included tamponade, PVR grade, a retinal detachment involving the 6 o'clock position and age as covariates, also showed no significant effect of tamponade choice on treatment success (OR 0.5, 95% 0.2-1.0, p = 0.10). CONCLUSION: We found no difference in treatment success with air tamponade versus fluorinated gas tamponades in the repair of primary retinal detachments, this also includes inferiorly located retinal tears and detachments.

Conjunctival melanoma in the Netherlands: a nationwide study.

PURPOSE: To evaluate risk factors for local recurrence, regional and distant metastases, and mortality associated with conjunctival melanoma. METHODS: This was a retrospective study of 194 patients with histologically confirmed conjunctival melanoma diagnosed between 1950 and 2002 in the Netherlands. Data were collected from all university centers and many nontertiary hospitals, using the National Pathology and the Leiden Oncologic Registration Systems. Based on the number of incidences, this study included 70% of the conjunctival melanomas in The Netherlands. Clinical and histopathological data for conjunctival tumors were reviewed and compared with data reported in the literature. Risk factors for local, regional, and distant metastases and survival were analyzed using the Kaplan-Meier and Cox regression analyses. RESULTS: Of 194 patients with conjunctival melanoma, 112 had a local recurrence (median, 1; range, 1-9) during follow-up (median, 6.8 years; range, 0.1-51.5). Location was the most important risk factor for development of local recurrence, and significantly more occurred with nonepibulbar (log rank, P=0.044) tumors. Significantly fewer local recurrences occurred with tumors initially treated with excision and adjuvant brachytherapy rather than with excision only (log rank, P=0.008) or with excision and cryotherapy (log rank, P <0.038). Forty-one (21%) patients had regional lymph node metastases, mostly to the parotid or preauricular lymph nodes (n=26; 13%). Risk factors for regional metastases were tumor thickness (log rank, P <0.001) and tumor diameter (log rank, P=0.010). Forty-nine (25%) patients (mean, 4.37 years) had development of distant metastases, mainly in the lung, liver, skin, and brain. Tumor-related survival was 86.3% (95% confidence interval [CI], 81.0-91.6) at 5 years, 72% (95% CI, 79.7-64.4) at 10 years, and 67% (95% CI, 58.9-76.1) at 15 years. The main mortality risk factors were nonepibulbar location (log rank, P <0.0001) and tumor thickness (log rank, P=0.0004). CONCLUSIONS: Nonepibulbar tumors more often recur locally and are associated with a shorter survival independent of other risk factors. Tumor thickness is also an important predictor of regional and distant metastases, as well as survival. A prospective study is needed to compare the effect of excision with radiotherapy and excision with cryotherapy on the number of local recurrences, exenteration rate, and survival.

Reflex and steady state tears in patients with latent stromal herpetic keratitis.

PURPOSE: To compare tear production in patients with stromal herpetic keratitis with that in healthy control subjects. METHODS: After instillation of 2 microL fluorescein into both eyes, the tear-fluorescein concentration was measured by fluorophotometry. During the first 10 minutes, steady state tear turnover (TTO-1) was determined. After a nasal alcohol stimulus to induce reflex tears, a second steady state tear turnover (TTO-2) was obtained during 15 minutes. The index of reflex lacrimation (IRL) was calculated as the percentage decrease in tear fluorescein concentration directly after the stimulus. TTO-1, TTO-2, and IRL were determined in the patients' affected eyes (n = 12), in the patients' healthy contralateral eyes, if possible (n = 9), and in one eye of healthy control subjects (n = 24). RESULTS: The TTO-1 in the affected and healthy eyes of patients was approximately two times lower than the TTO-1 in eyes of healthy control subjects (P = 0.012 and P = 0.024, respectively) and almost equal to the TTO-2 in eyes of healthy control subjects (P = 0.32 and P = 0.40). There were no significant differences in the values of TTO-1, IRL, and TTO-2 between affected and healthy eyes of patients (P > 0.5). IRL and TTO-2 did not differ significantly among the three groups (P > 0.5). CONCLUSIONS: Both eyes of the patients were dry. The dryness could be due to a defective reflex lacrimation under physiological conditions that can still be induced by nonphysiological nasal excitation. The cause of this may be demyelination of both trigeminal root entry zones as a result of a unilateral eye infection by the herpes virus. Another possibility is that dryness predisposes to herpetic infection or recurrent inflammation.

Predictive value of exfoliative cytology in pigmented conjunctival lesions.

PURPOSE: Pigmented lesions of the conjunctiva are often difficult to classify clinically. Exfoliative cytology may be helpful, but reliable data regarding the sensitivity and specificity of this test are currently lacking. We determined the value of exfoliative cytology with regard to pigmented conjunctival lesions. METHODS: A total of 294 smears from 182 patients were screened for malignancy within 6 months of exfoliative cytology. Smears were classified according to the following categories: grade 0 = insufficient material for diagnosis; grade 1 = normal conjunctival cells; grade 2 = melanocytes with mild atypia; grade 3 = melanocytes with moderate atypia, and grade 4 = melanocytes with severe atypia. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of exfoliative cytology were 85%, 78%, 59% and 93%, respectively. CONCLUSION: Exfoliative cytology is a fast, easy and non-invasive technique that may be used in the evaluation of patients with a pigmented conjunctival lesion.