Fundus imaging features of congenital rubella retinopathy.

PURPOSE: To evaluate the clinical characteristics of congenital rubella retinopathy (CRR) with modern fundus imaging. METHODS: Single-center case series. Eleven patients (2005-2020) at the Emory Eye Center with known or presumed CRR. Trained image readers reviewed fundus imaging (color fundus photography, widefield pseudocolor imaging, near-infrared reflectance imaging, autofluorescence imaging, and spectral-domain optical coherence tomography) for pre-specified features suggestive of CRR. RESULTS: Eleven patients with confirmed (63.6%) or presumed (36.3%) CRR were identified. All were female with median (range) age of 53 (35-67) years. Six (54.5%) were born during the 1964-1965 United States rubella epidemic. All had congenital hearing loss. Two (18.2%) had a congenital heart defect. Eleven (50.0%) eyes had salt-and-pepper retinal pigmentary changes. Twenty-two eyes (100.0%) had irregularly distributed regions of speckled hypoautofluorescence. One eye (4.5%) had a presumed macular neovascularization. CONCLUSION: Modern fundus imaging demonstrates characteristic features of CRR, even when pigmentary changes are not readily apparent on examination. Widefield autofluorescence findings of irregularly distributed speckled hypoautofluorescence are particularly revealing. This series of newly diagnosed adults with CRR may represent the milder end of the phenotypic spectrum of this condition, highlighting imaging findings that may aid in diagnostically challenging cases of CRR.

Secondary ocular malignancies: A review.

Secondary ocular malignancies most commonly spread to the choroid. Previously, the prognosis was poor however, with newer treatments including immunotherapy, patient's life expectancy have increased. It is therefore, important that ophthalmologists diagnose this condition in a timely manner and offer treatment to maximize visual potential and refer them on to oncology colleagues in order to optimize their systemic treatment for their primary cancer.

Approach to Cataract Surgery in an Ebola Virus Disease Survivor with Prior Ocular Viral Persistence.

A 46-year-old patient with previously documented Ebola virus persistence in his ocular fluid, associated with severe panuveitis, developed a visually significant cataract. A multidisciplinary approach was taken to prevent and control infection. Ebola virus persistence was assessed before and during the operation to provide safe, vision-restorative phacoemulsification surgery.

Intravitreous Cutaneous Metastatic Melanoma in the Era of Checkpoint Inhibition: Unmasking and Masquerading.

PURPOSE: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored. DESIGN: Multicenter, retrospective cohort study. PARTICIPANTS: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. METHODS: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye. MAIN OUTCOME MEASURES: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes. RESULTS: The median age at presentation of ophthalmic disease was 66 years (range, 23-88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5-38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30-40 Gy) in 6 eyes, intravitreous melphalan (10-20 µg) in 4 eyes, enucleation of 1 eye, and local observation while receiving systemic treatment in 2 eyes. Three eyes received intravitreous bevacizumab for neovascularization. The final Snellen visual acuity ranged from 20/20 to no light perception. CONCLUSIONS: The differential diagnosis of vitreous debris in the context of metastatic cutaneous melanoma includes intravitreal metastasis, and this seems to be particularly apparent during this era of treatment with checkpoint inhibition. External beam radiation, intravitreous melphalan, and systemic checkpoint inhibition can be used in the treatment of ophthalmic disease. Neovascular glaucoma and retinal detachments may occur, and most eyes show poor visual potential. Approximately one quarter of patients demonstrated ocular disease that preceded central nervous system metastasis. Patients with visual symptoms or vitreous debris in the context of metastatic cutaneous melanoma would benefit from evaluation by an ophthalmic oncologist.

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis.

PURPOSE: To examine the BRCA1-associated protein-1 (BAP1) expression of primary uveal melanomas without and with metastasis, and to analyze the correlation between the BAP1 immunoreactivity of primary uveal melanoma and other clinicopathologic features. DESIGN: Retrospective case series. PARTICIPANTS: Forty patients with uveal melanoma (mean age, 57.98±14.75 years) were included in this analysis, of whom 20 had no metastatic disease and 20 had metastasis. METHODS: Medical records and histology slides of patients with primary uveal melanoma treated by enucleation were reviewed. BAP1 expression was evaluated by immunohistochemical staining of formalin-fixed, paraffin-embedded sections. Immunoreactivity in the nucleus and cytoplasm were graded by estimating the percentage of primary tumor cells showing a positive staining of their nucleus or cytoplasm per 1 high-power field 200× (grades 0-3). MAIN OUTCOME MEASURES: Tumor size, histologic features, nuclear and cytoplasmic BAP1 immunoreactivity grade, and patient outcome, including development of metastasis. RESULTS: Significantly lower (P = 0.025) nuclear BAP1 immunoreactivity was observed in the metastatic melanoma group. Greater tumor thickness, basal diameter, and more advanced TNM stage were associated with an increased odds ratio of developing metastasis (P < 0.05). In addition, tumors with a higher proportion of cells expressing nuclear BAP1 had decreased odds of developing metastatic disease in a multivariate model (P = 0.042). Metastasis-free survival was significantly longer in patients with uveal melanoma with high nuclear BAP1 stain (P = 0.004). CONCLUSIONS: Time to metastasis differs in patients with primary uveal melanoma with different grades of nuclear BAP1 immunoreactivity. Nuclear BAP1 stain is the only significant independent predictor of metastatic disease in this study. Our data support the role of BAP1 immunohistochemical staining of primary uveal melanoma to evaluate metastatic risk.

Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature.

Indeterminate melanocytic proliferations of the conjunctiva have both benign and malignant features that previously made these lesions nearly impossible to categorize in existing classification schemes. With the evolution of immunohistochemistry and molecular genetics, however, subclassifications have emerged that allow for a more tailored diagnosis and management. These conjunctival melanocytic proliferations include deep penetrating nevus, granular cell nevus, and nevoid melanoma. There remains a small subset of conjunctival melanocytic proliferations that defy precise characterization as nevi, primary acquired melanosis, or melanomas despite currently available ancillary diagnostic modalities and remain indeterminate. We highlight these unusual types of nevi and melanomas, with an update on their morphologic, immunohistochemical, and molecular genetic characteristics.

IODINE-125 PLAQUE BRACHYTHERAPY FOR DIFFUSE CHOROIDAL HEMANGIOMA.

PURPOSE: To report 6 cases of diffuse choroidal hemangioma in children treated with iodine-125 plaque brachytherapy at a single tertiary care center. METHODS: Retrospective case series. RESULTS: Six pediatric patients diagnosed with diffuse choroidal hemangioma were included in the study. Preplaque visual acuity ranged from 20/150 to no light perception. All patients had extensive serous retinal detachment at presentation. An iodine-125 radioactive plaque was placed on the affected eye to administer a dose of 34.2-42.1 Gy to the tumor apex over a median of 4 days. Tumor regression and subretinal fluid resolution were observed in all eyes within 17 months of treatment. Visual acuity improved in two patients. Radiation-induced cataract and subretinal fibrosis were documented in one case, and one patient developed radiation retinopathy. No patients developed neovascular glaucoma within the follow-up time of 12-65 months. CONCLUSION: Iodine-125 plaque radiotherapy is an effective option for diffuse choroidal hemangioma, although there is a risk for radiation-induced complications.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

PURPOSE: Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. MATERIALS AND METHODS: This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). RESULTS: 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. CONCLUSION: In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

M2/M1 ratio of tumor associated macrophages and PPAR-gamma expression in uveal melanomas with class 1 and class 2 molecular profiles.

Macrophages have been found to be negative predictors of outcome in patients with uveal melanoma. In particular, recent studies point toward a disease-progressing role of proangiogenic M2 macrophages in melanomas with monosomy 3. Although most studies implicate a protective effect of PPAR-gamma activation in tumors, PPAR-gamma has also been shown to promote the polarization of M1 macrophages toward the M2 phenotype. The purpose of this investigation was first, to characterize the phenotype of tumor infiltrating macrophages and second, to study PPAR-gamma expression in uveal melanomas with molecular gene expression profile as prognostic predictors for patients' outcome. Twenty specimens from patients with uveal melanoma were analyzed for clinical and histologic tumor characteristics. The molecular RNA profile (class 1 or class 2) was commercially determined. Using immunohistochemical techniques, the specimens were dual labeled for CD68 and CD163. CD68 + CD163- M1 macrophages and CD68 + CD163+ M2 macrophages were analyzed in ten high power fields sparing macrophage-poor areas and a mean value was calculated for each tumor. The tumors were immunostained for von Willebrand factor and the micro vascular density (MVD) was analyzed according to Foss. To assess the proliferative rate of each tumor, Ki67 expression was evaluated in ten high power fields followed by calculation of a mean value. Expression of PPAR-gamma was evaluated using a score from 0 (no staining) to 3 (tumor entirely stained). Statistical analysis and a respective correlation were made between histologic characteristics, molecular profile, type of tumor infiltrating macrophages (M1 vs. M2), MVD, proliferative rate, and PPAR-gamma expression. Our results showed a correlation between the ratio of M2/M1 macrophages and the molecular profile with a ratio of approximately 1 corresponding to molecular class 1 and a ratio of approximately 2 corresponding to molecular class 2 (p = 0.01). The ratio of M2/M1 macrophages was higher in tumors with extraocular extension (p = 0.01). PPAR-gamma was predominantly expressed in the cytoplasm of tumor cells. Its expression showed no association with the molecular RNA profile (p = 0.83). This study confirmed that the ratio of M2/M1 macrophages is another prognostic factor in uveal melanoma. Thus, polarization of macrophages plays an important role for patients' outcome. PPAR-gamma is expressed in uveal melanoma tumor cells and further studies are warranted to determine its role in tumor biology.

CHOROIDAL OSTEOMA IN AN INFANT.

PURPOSE: To describe a case of choroidal osteoma with macular involvement in an infant that was treated with transpupillary thermotherapy. METHODS: A case report. RESULTS: An 11-month-old infant presented for retinopathy of prematurity follow up examination and was found to have a three disc-diameter round, orange, subretinal, slightly elevated lesion with well-defined margins in the superior macula of the left eye. B-scan ultrasonography showed a slightly elevated, highly reflective choroidal mass with acoustic shadowing. A diagnosis of choroidal osteoma was made. Six months later, repeat examination under anesthesia (EUA) showed the lesion to be increasing in size and encroaching on the fovea. Given demonstrated growth and the risk of central vision loss, the patient was treated with transpupillary thermotherapy (TTT). Subsequent EUAs, over a period of four months, have shown complete decalcification with no subsequent growth. CONCLUSION: Choroidal osteomas are benign lesions that can be sight threatening if located in the macula. TTT in this case resulted in complete regression of a sight threatening extrafoveal choroidal osteoma at four month follow up.

Conjunctival stromal tumor: report of 4 cases.

PURPOSE: To describe the clinical, histopathologic, immunohistochemical, and ultrastructural features of a case series of benign stromal tumors in the bulbar conjunctiva. DESIGN: Observational case series. PARTICIPANTS: Four patients with a conjunctival lesion that were classified histologically as low-grade stromal tumors consisting of spindle-shaped cells with occasional pseudonuclear inclusion and multinucleated cells in a partly myxoid matrix. METHODS: Four cases of low-grade conjunctival stromal tumors were retrospectively identified in an ophthalmic pathology laboratory database. Patients' records were analyzed for demographic data, clinical appearance, and the postoperative course. Formalin-fixed, paraffin-embedded specimens were routinely processed and stained with hematoxylin and eosin and periodic acid Schiff. Immunohistochemical stains for vimentin, S100, CD34, smooth muscle actin (SMA), CD68, and factor XIIIa were performed. Transmission electron microscopy (TEM) was performed on 3 of the cases. MAIN OUTCOME MEASURES: Histopathologic evaluation (including immunostains and TEM) and clinical correlation. RESULTS: All 4 tumors occurred in the bulbar conjunctiva of patients between 41 to 53 years of age. None of the patients developed recurrence after excisional biopsy. Histologically, all tumors exhibited spindle-shaped cells with pseudonuclear inclusions and occasional multinuclear cells. Mitotic figures were not observed. The stroma seemed to be myxoid to collagenous. Immunohistochemical stains were positive for CD34, vimentin, and focally for CD68, but were negative for S100 and SMA. CONCLUSIONS: We propose to classify these benign lesions, which share distinct histopathologic features, as "conjunctival stromal tumors." A reactive/inflammatory component needs to be considered in the pathogenesis of this lesion.

Diagnosis and management of an intraorbital vascular fistula.

A spontaneous intraorbital arteriovenous fistula is an extremely rare phenomenon. More commonly, arteriovenous fistulas occur spontaneously as carotid cavernous fistulas and dural cavernous fistulas or are secondary to trauma. Surgical approaches vary widely and each carries their own set of potential problems. The purpose of this single case report was to provide an example of a successful treatment of a rare, spontaneous intraorbital vascular fistula.

Foreign body giant cell reaction to silicone oil presenting as a salmon-patch conjunctival lesion.

Purpose: To describe a case of foreign body giant cell reaction to silicone oil that presented as a salmon-patch conjunctival lesion. Observations: An elderly female with prior retinal surgery and oil tamponade was referred for a salmon-patch lesion in the conjunctiva. Biopsy revealed multiple vacuolations and foreign body giant cells in the substantia propria, consistent with a foreign body reaction to silicone oil. Conclusion and importance: Silicone oil can elicit an inflammatory reaction in the conjunctiva that could mimic a neoplasm. Excessive leakage of oil into the subconjunctival space should be avoided to prevent this complication.

Intraocular Lens and Lens Capsule Spread of Iridociliary Melanoma: Clinical and Histopathologic Features of 2 Cases.

Purpose: The aim of this study was to describe 2 patients with intraocular lens (IOL) and lens capsule spread of iridociliary melanoma. Methods: Two pseudophakic patients with iridociliary body melanoma that spread onto the surface of their IOL and remaining lens capsule were included. Their eyes were enucleated and the histopathologic features were evaluated. Results: Case 1 was an 82-year-old woman with diffuse primary iridociliary melanoma affecting the iris, lens capsule, IOL surface, and ciliary body. Case 2 was a 68-year-old female who developed melanoma recurrence in the anterior segment after plaque brachytherapy for iridociliary melanoma. The melanoma in both cases grew as a pigmented membrane onto the surface of the IOL. Conclusions: IOL and lens capsule spread of iridociliary melanoma can occur primarily or develop secondarily after plaque brachytherapy of a pseudophakic eye. Since the extent of the melanoma may be uncertain and there is a high likelihood of glaucoma, enucleation is a reasonable option.

Unilateral Xanthocoria and Retinal Vascular Anomalies in a 3-Year-Old Boy: Retinoblastoma or Coats Disease?

The authors describe a challenging case of unilateral retinoblastoma in a patient referred for xanthocoria. A 3-year-old boy was referred for unilateral xanthocoria and disordered retinal vasculature, suggestive of Coats disease. Further investigation revealed diffuse subretinal tumor seeding and areas of calcification, consistent with retinoblastoma. Enucleation was performed and histopathology confirmed exophytic retinoblastoma. This case highlights that xanthocoria, although often encountered in patients with Coats disease, can sometimes be associated with retinoblastoma. As such, retinoblastoma should be considered in the differential diagnosis for children with both leukocoria and xanthocoria. [J Pediatr Ophthalmol Strabismus. 2022;59(X):e32-e34.].