Primary acquired melanosis/melanoma: utility of conjunctival map biopsy.

AIM: To assess the role of map biopsy in patients with conjunctival primary acquired melanosis (PAM)/melanoma. METHODS: Retrospective case series of 400 conjunctival biopsy samples of 51 unique patients in a tertiary referral centre. RESULTS: Each patient underwent one diagnostic biopsy and several additional map biopsies (range 2-7) providing a total of 400 samples for the analysis (55 diagnostic biopsies, 345 map biopsies). The median age was 63 years old (range 20-88) with women representing 67% of the cases. Histopathological findings were graded as negative for melanosis/normal (grade 0), melanosis without atypia (grade 1), melanosis with mild atypia (grade 2), melanosis with severe atypia (grade 3) or invasive melanoma (grade 4). Clinicopathologic concordance was observed in the majority of the map biopsies (313, 91%) (positive: clinical+/path+ (57,17%), negative: clinical-/path- (256, 74%)). Three discordant samples (clinical-/path+) represented PAM sine pigmento. The histopathological spectrum of atypia was absent (40, 73%) or limited (11, 20%) in the majority of cases with tendency to cluster as low-grade or high-grade atypia. Map biopsy led to the identification of six patients (11%) with severe atypia, requiring topical mitomycin (MMC). Similarly, in 29 cases, periodic observation without topical MMC was recommended. One case of invasive melanoma transformation occurred in the MMC-treated group. CONCLUSIONS: Map biopsy enhances overall assessment of the anatomic and pathologic extent, impacting use of adjuvant topical chemotherapy. In absence of map biopsy, it would be impossible to diagnose PAM sine pigmento. Additional corroborative work is needed to validate our observations.

Choroidal macrovessel: Systematic review and analysis of anatomic origin.

There are various hypotheses for the anatomic origin of a choroidal macrovessel. We assess whether a choroidal macrovessel is a dilated posterior ciliary artery. A systematic review of published literature on choroidal macrovessels was performed with two additional cases from our institution. We compared the visible entry and vascular course of the macrovessel in the published literature. We performed a comparative analysis using indocyanine green angiography, swept source optical computed tomography, and 3D reconstruction of two choroidal macrovessels using 3D Slicer (Harvard, Boston, USA, https://www.slicer.org/). From the 14 studies found, 18 cases met inclusion criteria. The reported literature and our two cases showed a radiating course along a sectoral distribution pattern of either short or long posterior ciliary arteries. Our review of literature and 3D reconstruction analysis support the hypothesis that choroidal macrovessels are dilated posterior ciliary arteries.

Intravenous Chemotherapy for Retinoblastoma in the Era of Intravitreal Chemotherapy: A Systematic Review.

PURPOSE: The published data on ocular survival following intravenous chemotherapy of retinoblastoma (RB) seems to be skewed by evolving practice patterns induced by use of intravitreal chemotherapy (iVitc). We aimed to explore potential role of iVitc for vitreous seeding for patients treated with intravenous chemotherapy (IVC). METHODS: A literature search was performed to identify cases of RB treated with primary IVC prior to advent of iVitc by various search engines (PubMed, Medline, and Google) from 1992 to 2018. Studies were excluded if number of cases were less than 40 or lacked data related to type of recurrence and its treatment. Rates and patterns of recurrence and its management were categorized. RESULTS: Out of 15 studies identified, only 10 studies (797 eyes) met the inclusion criteria. The mean age at presentation was 15.3 months (range 0-192.8 months). Unilateral cases represented 25% of the cohort. The ocular survival rate with primary IVC was 63% (500/797 eyes). Of the 297 eyes (37%) that failed IVC therapy, additional 99 eyes could be salvaged with EBRT (599/797 eyes, 75%). Remaining 198 eyes were enucleated (198/797 eyes 25%). K-M survival analysis could not be done due lack of sufficient data. Recurrences that occurred (mean 12.2 months) after completion of primary IVC included relapse of retinal tumor (143 eyes [48%]), vitreous seeding (73 eyes [25%]), subretinal seeding (49 eyes [16%]), or any combination (103 eyes [35%]). Out of 73 eyes with vitreous seeding, additional 66 eyes (90%) would have been salvaged with iVitc, potentially improving ocular survival rates to 71% (500 + 66/797). CONCLUSIONS: Evolving practice patterns of RB treatment have unfavorably skewed published ocular survival rates following IVC. With incorporation of iVitc, the ocular survival rates with IVC can be potentially improved to be non-inferior to those achieved with intra-arterial chemotherapy.

Retinoblastoma in twins: Risk assessment of genotypic variants.

Purpose: To describe methods of risk assessment in twins with retinoblastoma (RB). Methods: A case series of four RB probands with a twin sibling. Family status, clinical presentation, and RB1 germline status-based risk assessment were analyzed. Results: Two pairs had a positive family history (unilateral and bilateral RB in one of the parents (#1 and #2, respectively) and two pairs (#3 and #4) were sporadic. One of the familial twins (#1) had a high risk (90%) of manifesting RB in the twin. The other case (#2) with an absent RB1 germline mutation in the twin had a 0% risk of developing RB. Among sporadic cases of twins (#3), genetic testing did not identify a germline mutation (tumor sample unavailable) in the proband which downgraded the risk of germline mutation from 15% to <1%. The twin never developed RB (5 years of age at last follow-up). Pathogenic mosaicism for germline RB1 mutation (c.1723C>T) could be identified (tumor tissue available) in the proband (# 4). Identical germline mutation (and RB tumor) was also noted in the twin. In each case, there was concordance between the assessed risk and manifestation of RB. Conclusion: Assessment of risk of RB in a twin presents with a unique challenge. Depending upon the genotype variant, the risk of developing RB can vary from 0% to 90%. In addition to family history, clinical manifestation in the proband, zygosity status, and RB1 germline status are critical in formulating risk-appropriate surveillance guidelines.

Ocular surface squamous neoplasia: outcomes following primary excision with 2 mm margin and cryotherapy.

PURPOSE: To assess margins and the rate of local recurrence of ocular surface squamous neoplasia after excision with a 2 mm margin and cryotherapy at a single ophthalmic oncology center. OUTCOME MEASURES: (1) Conjunctival margin were assessed as positive, negative, or indeterminate margins. (2) Feasibility of repair without a graft. (3) Local recurrence. METHODS: Retrospective chart review of histologically proven conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma cases that underwent excision with a 2 mm margin and cryotherapy. RESULTS: Eighty cases met inclusion criteria for the quantitative analysis. The margin was positive in six cases (7.5%), four of which were treated with post-op topical immunotherapy/chemotherapy. Of the six positive margin cases, there was one recurrence which occurred in the patient who did not receive post-op topical adjuvant therapy, however resolved after starting topical treatment. Conjunctival repair without use of a graft was feasible in 74 (93%) cases with a mean basal diameter of 6.4 mm. Total number of local recurrence was seen in three cases (4%), which were successfully treated with adjuvant topical treatment (one positive margin case, one indeterminate margin case) or repeat resection followed by episcleral plaque brachytherapy (one negative margin case). CONCLUSION: Excision with 2 mm margin of OSSN is not associated with high rates of positive surgical margins. Even those with positive margins, when treated with adjuvant topical therapy did not develop recurrence. While achieving low rates of local recurrence, the conjunctiva is conserved, thereby minimizing the need for amniotic membrane or free conjunctival grafts for conjunctival repair.

Photodynamic therapy for choroidal melanoma: What is the response rate?

To determine the response rate of choroidal melanoma following primary photodynamic therapy, we conducted a meta-analysis of published studies. A total of 7 studies reporting photodynamic therapy as primary treatment of choroidal melanoma in 162 patients with a mean tumor height of 2.8 mm (1.4 to 4.2) were identified. Forty-six percent of tumors were amelanotic, 48% were fully pigmented, and 6% had partial pigmentation. The photodynamic therapy parameters in all studies included 10-minute intravenous infusion of verteporfin (6 mg/m2), but varied in number of sessions (1 to 3), fluence (1× to 19×), and number of spots (single or multiple). The response was defined as tumor regression (partial or total) or lack of growth after initial treatment. The response to photodynamic therapy was predominantly observed as regression (126 [78%]). Overall response rate was 80% (mean) with a wide range among studies (58%-100%) over a period of 50 months (mean) with variable follow-up (range, 1-156 months). None of the studies reported progression- or recurrence-free survival; however, the recurrence rate was not related to the follow-up duration. Favorable prognostic factors were smaller size and lack of pigmentation. The overall response rate of 80% suggests that photodynamic therapy may be an effective primary treatment for small choroidal melanoma, especially in cases without pigmentation. Artifacts in study design (inclusion criteria and outcome measure) may have contributed to the variable observed response rate. Further studies with uniform inclusion criteria, standardized treatment parameters, well-defined outcome measures, and long follow-up are needed.

VITREOUS SEEDING OF CHOROIDAL MELANOMA.

PURPOSE: To report a case of vitreous seeding in a medium-sized choroidal melanoma and review the literature. METHODS: Observational case report and review of literature for pathogenesis, role of vitreous biopsy, and treatment outcomes. RESULTS: A case of 57-year-old man diagnosed with vitreous seeding in the left eye 1 year after episcleral brachytherapy for medium-sized choroidal melanoma. The patient was initially diagnosed to have subretinal and vitreous hemorrhage due to rupture of a retinal artery macroaneurysm for which focal laser and intravitreal antivascular endothelial growth factor injections were administered. Over the next 9 months, the vitreous hemorrhage cleared and choroidal melanoma with retinal invasion became evident. One year after brachytherapy, the primary tumor regressed with resolution of surrounding subretinal fluid and hemorrhage. However, gradual decline in the visual acuity from 20/50 to 20/500 with increase of pigmented debris over the retinal surface and in the vitreous cavity was noted. A vitreous biopsy confirmed the presence of viable melanoma cells (epithelioid type), and the eye was enucleated. Histopathology showed microscopic persistence of primary tumor with diffuse vitreous seeding. CONCLUSION: Vitreous seeding of choroidal melanoma poses a diagnostic and management challenge.

Chemotherapy for Retinoblastoma: Impact of Intravitreal Chemotherapy.

ABSTRACT: Chemotherapy is now the primary treatment of retinoblastoma in eyes with visual potential or those that are considered not advanced for retinoblastoma. In addition to intravenous chemotherapy (IVC), drugs delivered via alternative routes such as intra-arterial and intravitreal administration have emerged as promising options for management of retinoblastoma. Various studies have shown excellent results in salvaging nearly 100% of groups A-C eyes; however, intra-arterial chemotherapy (IAC) seems to offer superior local control rates as compared with IVC for advanced intraocular retinoblastoma (groups D and E eyes). Intravitreal chemotherapy (IVitC), that delivers the highest concentration of drug in the vitreous cavity while minimizing systemic drug concentration, has emerged in recent years (2012) as an effective treatment for refractory or persistent vitreous seeding. The role of concomitant and subsequent therapies is an important consideration, particularly the use of IVitC in combination with IAC. As IVitC became acceptable during the era of IAC, most of the patients treated previously with IVC did not receive IVitC. Therefore, it is possible that some of the IVC failures could have been avoided with the use of IVitC. We provide our perspective of published data that seems to be skewed by evolving practice patterns that project enhanced efficacy of IAC when compared with historic control rates achieved with IVC. In absence of better-quality data or randomized controlled trials, it is hard to establish superiority of one treatment over the other.

Intraocular Tumors: Angiographic Patterns.

Intraocular tumors are primarily diagnosed clinically. However, ancillary tests such as fluorescein angiogram provides excellent visualization of retinal tumors while indocyanine green angiography reveals intrinsic vascular patterns of choroidal tumors. In this review, we contrast angiographic patterns of a variety of retinal, choroidal, and iris tumors.

Isolated Diffuse Choroidal Hemangioma: A Variant of Sturge-Weber Syndrome?

The authors report a case of a diffuse choroidal hemangioma in the left eye of a 17-year-old girl. No evidence of leptomeningeal angiomatosis was found on magnetic resonance imaging and neither the medical history nor the clinical examination revealed a port wine birthmark on the left side of the face. Fine telangiectatic vessels were found on the bulbar conjunctiva of the ipsilateral eye. Because of the shared destination of the vessel-trigeminal-ectoderm complex that migrates toward the optic placode, forming choriocapillaris, upper facial skin (upper eyelid), and conjunctival vessels, an embryological basis can be offered for ophthalmic angiomatosis of Sturge-Weber syndrome. The authors propose that vascular angiomatosis of upper eyelid skin and conjunctiva are phenotypically equivalent and may be present or absent, independent of each other. Their proposed expansion of Sturge-Weber syndrome diagnostic criteria needs to be validated by a comprehensive review of ophthalmic features of Sturge-Weber syndrome. [J Pediatr Ophthalmol Strabismus. 2020;57:e43-e47.].

Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): Report of the Clinical Spectrum of 3 Cases.

PURPOSE: To report 3 cases providing insight into clinical progression of reactive retinal astrocytic tumor. METHODS: The clinical, imaging, and when available, the cytologic features of 3 cases of reactive retinal astrocytic tumor (focal nodular gliosis) were reviewed. RESULTS: A 6-year-old female, a 49-year-old man, and a 39-year-old man each developed a white retinal mass associated with laser photocoagulation, lattice degeneration, and treatment of a presumed vascular tumor, respectively. All tumors were white, circumscribed retinal masses that tended to be associated with exudation and either initially or eventually minimal vascularity. CONCLUSION: Reactive retinal astrocytic tumor can be observed in response to a degenerative, inflammatory, or ischemic retinal insult. Such tumors may progress after therapeutic intervention.