Histopathological Risk Features in Primary and Secondary Enucleation for Group D Retinoblastoma: A Clinicopathological Correlation Study

Background and objective Group D retinoblastoma (RB) represents advanced intraocular disease with a substantial risk of treatment failure. Although globe-sparing therapies have improved ocular salvage rates, there is limited knowledge regarding the histopathological risk profile of enucleated Group D eyes, particularly when enucleation is performed after failed conservative treatment. This study aimed to evaluate the presence of high-risk histopathological features in Group D eyes undergoing primary versus secondary enucleation. Methods This study was designed as a focused secondary histopathological analysis of enucleated eyes from a previously reported cohort of Group D RB patients managed at a tertiary care center. Eight eyes underwent enucleation: four (50%) underwent primary enucleation due to advanced disease at presentation, and four (50%) underwent secondary enucleation following the failure of globe-sparing therapy. All specimens were examined for high-risk histopathological features, including post-laminar optic nerve invasion, optic nerve cut-end involvement, massive choroidal invasion, and scleral invasion. Fisher's exact test was used, and odds ratios (OR) with confidence intervals (CI) were calculated to explore differences between the groups. Results High-risk histopathological features were identified in four of eight eyes (50%). One of the four eyes that underwent primary enucleation (25%) demonstrated high-risk features, compared with three of the four eyes that underwent secondary enucleation (75%). Fisher's exact test showed no statistically significant association between enucleation timing and high-risk pathology (p = 0.49). The OR indicated lower odds of high-risk pathology with primary enucleation (OR: 0.11; 95% CI: 0.005-2.73), although the confidence intervals were wide due to the small sample size. Conclusions High-risk histopathological features were more frequently observed in Group D RB eyes undergoing secondary enucleation after failed globe-sparing therapy. These findings suggest that delaying enucleation may allow the progression of microscopic disease that is not clinically apparent and highlight the importance of timely enucleation in selected advanced cases. This clinicopathological correlation complements reported clinical outcomes and supports careful risk assessment when considering globe-sparing approaches in Group D disease.