Swathi Kaliki

High-Risk Retinoblastoma Based on International Classification of Retinoblastoma: Analysis of 519 Enucleated Eyes

PURPOSEnTo determine the correlation between the International Classification of Retinoblastoma (ICRB) and histopathologic high-risk retinoblastoma.nnnDESIGNnRetrospective study.nnnPARTICIPANTSnA total of 519 patients.nnnINTERVENTIONnPrimary enucleation.nnnMAIN OUTCOME MEASURESnHigh-risk retinoblastoma, metastasis, and death.nnnRESULTSnOf 519 primarily enucleated eyes, 87 (17%) were classified as group D and 432 (83%) were classified as group E on the basis of the ICRB. High-risk retinoblastoma was identified in 23% (117/519) of enucleated eyes, including 17% (15/87) group D and 24% (102/432) group E eyes. High-risk histopathologic features of retinoblastoma included anterior chamber involvement (5/15 [33%] group D eyes, 31/102 [30%] group E eyes), isolated massive posterior uveal invasion ≥ 3 mm (7/15 [47%] group D eyes, 22/102 [22%] group E eyes), isolated post-laminar optic nerve invasion (2/15 [13%] group D eyes, 46/102 [45%] group E eyes), and any combination of posterior uveal invasion and optic nerve involvement (7/15 [47%] group D eyes, 37/102 [36%] group E eyes). On logistic regression analysis, massive posterior uveal invasion ≥ 3 mm was more common in group D eyes (P = 0.0442), and post-laminar optic nerve invasion was more common in group E eyes (P = 0.0390). Of 117 patients with high-risk retinoblastoma, systemic adjuvant chemotherapy was administered in 83 patients (71%). Systemic metastasis developed in 0% (0/15) of those with high-risk group D retinoblastoma and 10% (10/102) of those with high-risk group E retinoblastoma over a mean follow-up period of 78 months (median, 62 months; range, 1-419 months). There was no metastasis in any patient (n = 402) classified with non-high-risk retinoblastoma. Of the 10 patients who developed metastasis, 4 had received prior adjuvant chemotherapy and 6 had no prior adjuvant chemotherapy. There was no metastasis in high-risk patients treated with vincristine sulphate, etoposide phosphate, and carboplatin (VEC). Death from metastasis occurred in 4% of high-risk patients (5/117).nnnCONCLUSIONSnOn the basis of the ICRB, 17% of group D and 24% of group E eyes are at increased risk for metastatic disease. In this study, 8% of patients developed metastasis. There was no metastasis in any patient classified with non-high-risk retinoblastoma.nnnFINANCIAL DISCLOSURE(S)nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intravitreal Melphalan for Persistent or Recurrent Retinoblastoma Vitreous Seeds: Preliminary Results

IMPORTANCEnRecurrent or persistent vitreous seeds following treatment of retinoblastoma poses difficult management and often leads to enucleation.nnnOBJECTIVEnTo describe the technique and evaluate the efficacy and complications of intravitreal melphalan for vitreous seeding from retinoblastoma.nnnDESIGN, SETTING, AND PARTICIPANTSnThis retrospective noncomparative analysis was conducted at a tertiary referral center. The study included 11 consecutive eyes of 11 patients with viable persistent or recurrent vitreous seeds following treatment of retinoblastoma.nnnINTERVENTIONSnAll eyes received intravitreal melphalan injection (20-30 µg) by transconjunctival pars plana route with concomitant triple-freeze cryotherapy at the injection site during needle withdrawal for prevention of extraocular seeding. Each patient was offered planned 6 monthly cycles.nnnMAIN OUTCOMES AND MEASURESnVitreous seed control and complications of therapy.nnnRESULTSnThe mean patient age at vitreous injection was 37 months (median, 27 months; range, 16-82 months). Viable vitreous seeds involved 2 (n = 1), 3 (n = 4), or 4 (n = 6) quadrants. The solid intraretinal retinoblastoma and subretinal seeds showed regression in all eyes following intravenous chemotherapy (n = 6) or intra-arterial chemotherapy (n = 5). There were a total of 55 injections, with a mean number per patient of 5 (median, 6; range, 2-6). Fewer than 6 injections (n = 5) were delivered owing to complete vitreous seed control and parental desire to avoid more injections. By a mean of 9 months follow-up (median, 9 months; range, 6-16 months), therapeutic success with complete vitreous seed regression was achieved in all 11 cases (100%). Globe salvage was attained in all cases (100%). Further vitreous seed development did not occur in any case. Complications included focal retinal pigment epithelial mottling near the site of chemotherapy injection (2 eyes) and nonaxial posterior lens opacity (2 eyes). There was no case of extraocular tumor extension, hypotony, or phthisis bulbi.nnnCONCLUSIONS AND RELEVANCEnThese preliminary short-term results suggest that intravitreal melphalan injection for persistent or recurrent vitreous retinoblastoma seeding can provide tumor control with minimal toxicity and complications.

Enhanced Depth Imaging Optical Coherence Tomography of Choroidal Nevus in 104 Cases

PURPOSEnTo describe the characteristics of choroidal nevus using the enhanced depth imaging (EDI) feature of spectral-domain optical coherence tomography (OCT).nnnDESIGNnRetrospective, observational case series.nnnPARTICIPANTSnOne hundred four eyes with choroidal nevus.nnnMETHODSnSpectral-domain EDI OCT was performed with a Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) using a custom scan acquisition protocol of up to 13 raster lines of 9-mm scan length with automatic real-time image averaging set at 100 images. The thickness of choroidal nevus was measured by combining Heidelbergs autosegmentation with manual segmentation.nnnMAIN OUTCOME MEASURESnImaging features and thickness correlation of choroidal nevus by EDI OCT versus standard ultrasonography.nnnRESULTSnOf 104 eyes with choroidal nevus imaged with EDI OCT, 51 (49%) displayed image detail suitable for study. The remaining 53 cases were suboptimal because of statistically identified factors of age older than 60 years (P = 0.027), female gender (P = 0.008), extramacular location of nevus (P<0.001), mean distance from foveola more than 3 mm (P = 0.002), mean distance from optic disc more than 4 mm (P<0.001), and mean maximal basal diameter more than 5 mm (P = 0.006). Of the 51 suitable cases, mean nevus thickness was 685 μm (median, 628 μm; range, 184-1643 μm) by EDI OCT compared with 1500 μm (median, 1500 μm; range, 1000-2700 μm) by ultrasonography. The most common EDI OCT imaging features included partial (59%) or complete (35%) choroidal shadowing deep to the nevus, choriocapillaris thinning overlying the nevus (94%), retinal pigment epithelial (RPE) atrophy (43%), RPE loss (14%), RPE nodularity (8%), photoreceptor loss (43%), inner segment-outer segment junction (IS-OS) irregularity (37%), IS-OS loss (6%), external limiting membrane irregularity (18%), outer nuclear and outer plexiform layer irregularity (8%), and inner nuclear layer irregularity (6%). Overlying subretinal fluid was identified by EDI OCT (16%), ophthalmoscopic examination (8%), and ultrasonographic evaluation (0%). A comparison of pigmented versus nonpigmented nevus showed only 1 significant difference of more intense choroidal shadowing with pigmented nevus (P = 0.046).nnnCONCLUSIONSnImaging of choroidal nevus with EDI OCT enables precise measurement of tumor thickness with comparatively reduced thickness relative to ultrasonography. Using EDI OCT, 94% of choroidal nevi were found to have overlying choriocapillaris thinning.

Ciliary Body Medulloepithelioma: Analysis of 41 Cases

PURPOSEnTo describe the clinical features, histopathology, treatment, and outcomes of ciliary body medulloepithelioma.nnnDESIGNnRetrospective study.nnnPARTICIPANTSnForty-one patients with medulloepithelioma.nnnINTERVENTIONnCryotherapy, plaque radiotherapy, external beam radiotherapy, tumor removal by partial lamellar sclerouvectomy (PLSU), or enucleation.nnnMAIN OUTCOME MEASURESnMetastasis and death.nnnRESULTSnOf 41 patients with ciliary body medulloepithelioma, the median age at diagnosis was 5 years. The mean tumor basal diameter was 11 mm, and the mean tumor thickness was 7 mm. Related features included secondary glaucoma (n = 18, 44%), iris neovascularization (n = 21, 51%), cataract (n = 19, 46%), lens subluxation (n = 11, 27%), lens coloboma (n = 8, 20%), retrolental neoplastic cyclitic membrane (n = 21, 51%), intratumoral cysts (n = 25, 61%), and extraocular extension (n = 4, 10%). There was systemic association with pleuropulmonary blastoma in 2 cases (5%). Primary tumor treatment included enucleation (n = 21, 60%), tumor removal by PLSU (n = 8, 23%), plaque radiotherapy (n = 3, 9%), external beam radiotherapy (n = 1, 3%), cryotherapy (n = 1, 3%), or palliative chemotherapy (n = 1, 3%). In 1 case, medulloepithelioma was diagnosed histopathologically after inadvertent evisceration for blind painful eye. Subsequent treatment for residual or recurrent tumor in cases treated conservatively/inappropriately (n = 15) was necessary in 7 cases (47%). Histopathology disclosed benign features in 6 cases (20%), malignant features in 24 cases (80%), teratoid features in 11 cases (37%), and nonteratoid features in 19 cases (63%). In the 26 enucleated eyes, other features included retrolental neoplastic cyclitic membrane (n = 18, 69%), neoplastic epiretinal membrane (n = 6, 23%), and persistent hyaloid artery (n = 6, 23%). Systemic metastasis occurred in 3 cases (8%) over a mean follow-up of 49 months, all of whom presented with extrascleral extension of tumor due to mean delay in diagnosis by 39 months.nnnCONCLUSIONSnMedulloepithelioma most commonly occurs in children. Systemic association with pleuropulmonary blastoma rarely is found. Patients with extrascleral medulloepithelioma are at risk for metastasis.

Giant ocular surface squamous neoplasia managed with interferon alpha-2b as immunotherapy or immunoreduction.

OBJECTIVEnTo evaluate the efficacy of interferon alpha-2b (IFNα2b) for extensive ocular surface squamous neoplasia (OSSN).nnnDESIGNnRetrospective, interventional case series.nnnPARTICIPANTSnEighteen eyes in 18 patients.nnnMETHODSnEach patient with giant OSSN (a single tumor ≥15 mm basal diameter or ≥6 limbal clock-hours) was managed with topical IFNα2b (1 million IU/ml) 4 times daily or with injection IFNα2b (a portion of 10 million IU/ml vial) with follow-up every 1 to 3 months.nnnMAIN OUTCOME MEASURESnTumor response, recurrence, and treatment complications were evaluated.nnnRESULTSnEighteen patients with giant OSSN (median diameter [MD], 20 mm; median clock-hours [MCH], 6) were treated with topical IFNα2b (n = 12), injection IFNα2b (n = 3), or both (n = 3). The IFNα2b achieved complete tumor control (immunotherapy) in 13 eyes and partial tumor control with reduction in size (immunoreduction) in 5 eyes. Topical IFNα2b alone (n = 12) provided complete immunotherapy in 7 eyes (MD, 12 mm; MCH, 9) over a median period of 5 months and immunoreduction by 74% in 5 eyes (MD, 20 mm; MCH, 3), allowing for subsequent surgical excision (n = 3), photodynamic therapy (n = 1), or cryotherapy (n = 1) for tumor control. Injection IFNα2b alone (n = 3; median, 1 injection) provided complete control of giant tarsal conjunctival OSSN (MD, 20 mm) over a 1-month period. A combination of topical and injection IFNα2b (n = 3; median, 3 injections) completely resolved larger tumors (MD, 30 mm; MCH, 6) over a 6-month period. Complications of IFNα2b included transient flu-like symptoms (n = 3), corneal epithelial defect (n = 2), and conjunctival hyperemia (n = 1). During a median follow-up of 11 months, there were no tumor recurrences, but 2 new tumors appeared at a remote site from the original tumor, requiring operative intervention.nnnCONCLUSIONSnIn 72% of giant OSSNs IFNα2b achieved complete control (immunotherapy); there was a reduction in size (immunoreduction) in 28% of giant OSSNs.

Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes.

IMPORTANCEnOcular/oculodermal (oculo[dermal]) melanocytosis is a congenital periocular pigmentary condition that can lead to the development of uveal melanoma, estimated at 1 in 400 affected patients. In this study, patients with melanocytosis who developed uveal melanoma were found to have double the risk for metastasis compared with those without melanocytosis.nnnOBJECTIVEnTo determine the relationship of oculo(dermal) melanocytosis to the prognosis of patients with uveal melanoma.nnnDESIGN, SETTING, AND PATIENTSnRetrospective chart review of 7872 patients with uveal melanoma treated at the Ocular Oncology Service, Wills Eye Institute, from August 25, 1970, through August 27, 2008.nnnEXPOSURESnEnucleation, plaque radiotherapy, local resection, or thermotherapy.nnnMAIN OUTCOMES AND MEASURESnMetastasis and death.nnnRESULTSnOf 7872 patients with uveal melanoma, oculo(dermal) melanocytosis was present in 230 (3%). The melanocytosis involved the sclera (92%), iris (17%), choroid (12%), eyelid (8%), and temporal fossa (1%). Eyes with melanoma and oculo(dermal) melanocytosis had a relative risk for metastasis 1.6 times greater compared with those with no melanocytosis (P < .001). Metastasis of uveal melanoma was 2.8 times higher in patients with iris melanocytosis (P < .001), 2.6 times higher with choroidal melanocytosis (P = .02), and 1.9 times higher with scleral melanocytosis (P < .001). By Kaplan-Meier estimates, metastasis in patients with oculo(dermal) melanocytosis vs no melanocytosis was 2% vs 1.8% at 1 year, 27% vs 15% at 5 years, and 48% vs 24% at 10 years (P < .001). By multivariable analysis, the factors predictive of metastasis in patients harboring uveal melanoma associated with oculo(dermal) melanocytosis were increased tumor thickness (P = .001) and the presence of subretinal fluid (P = .05), and the only factor predictive of death was increased tumor thickness (P = .009). CONCLUSIONS AND RELEVANCE Patients with uveal melanoma associated with oculo(dermal) melanocytosis have double the risk for metastasis compared with those with no melanocytosis. All patients with oculo(dermal) melanocytosis should undergo ophthalmic examination and imaging on a twice-yearly basis because this could help with the early detection of melanoma.

Iris melanoma: Features and prognosis in 317 children and adults

PURPOSEnTo evaluate iris melanoma in children versus adults.nnnMETHODSnRetrospective, nonrandomized clinical case series including all patients with a clinical diagnosis of iris melanoma managed at the Ocular Oncology Service at Wills Eye Institute over 40 years. Patients were divided into three age categories based on age at presentation: children (≤ 20 years), mid-adults (21-60 years), and older adults (>60 years). The clinical features, treatments, and outcomes were statistically analyzed based on patient age at presentation. The main outcome measures were melanoma features and related metastasis and death.nnnRESULTSnOf 8,101 eyes with uveal melanoma, there were 317 (4%) with iris melanoma, including 24 (8%) children (≤ 20 years), 187 (59%) mid-adults (21-60 years), and 106 (33%) older adults (>60 years). There was no age-related difference in race, sex, tumor quadrant, thickness, pigmentation, associated corectopia, ectropion uveae, hyphema, or extraocular extension. Significant age-related differences were found with mean tumor basal diameter, tapioca appearance, mean intraocular pressure, secondary glaucoma, tumor seeding in angle, and mean number of clock hours of angle seeding. Multivariate analysis of factors predictive of metastasis included extraocular extension and high intraocular pressure. Factors predictive of death included increased tumor thickness and high intraocular pressure. There was no difference in metastasis or death by age group.nnnCONCLUSIONSnIris melanoma shows significant clinical differences in children versus adults, with smaller tumor size, less tumor seeding in angle, and lower incidence of secondary glaucoma. There was no significant difference in metastasis or death by age group.

Lesions Simulating Retinoblastoma (Pseudoretinoblastoma) in 604 Cases : Results Based on Age at Presentation

PURPOSEnTo determine the types and frequency of ocular conditions that simulate retinoblastoma (pseudoretinoblastoma) based on age at presentation.nnnDESIGNnRetrospective case series.nnnPARTICIPANTSnTwo thousand seven hundred seventy-five patients.nnnMETHODSnChart review.nnnMAIN OUTCOME MEASURESnConditions simulating retinoblastoma.nnnRESULTSnOf 2775 patients referred for management of retinoblastoma, 2171 patients (78%) had confirmed retinoblastoma and 604 patients (22%) had simulating lesions (pseudoretinoblastomas). In the pseudoretinoblastoma cohort, the mean patient age at presentation was 4 years (median, 2 years). There were 27 different pseudoretinoblastoma conditions, and the 10 most common included Coats disease (n = 244; 40%), persistent fetal vasculature (PFV; n = 158; 28%), vitreous hemorrhage (n = 27; 5%), ocular toxocariasis (n = 22; 4%), familial exudative vitreoretinopathy (FEVR; n = 18; 3%), rhegmatogenous retinal detachment (n = 18; 3%), coloboma (n = 17; 3%), astrocytic hamartoma (n = 15; 2%), combined hamartoma of retina and retinal pigment epithelium (n = 15; 2%), and endogenous endophthalmitis (n = 10; 2%). Simulating lesions differed based on age at presentation, and children younger than 1 year were most likely to have PFV (49%), Coats disease (20%), or vitreous hemorrhage (7%); those 2 to 5 years of age were most likely to have Coats disease (61%), toxocariasis (8%), or PFV (7%); and those older than 5 years were most likely to have Coats disease (57%), toxocariasis (8%), or FEVR (6%).nnnCONCLUSIONSnThe most common pseudoretinoblastomas include Coats disease, PFV, and vitreous hemorrhage, but the spectrum varies depending on patient age.

Photodynamic Therapy for Choroidal Metastasis in 8 Cases

PURPOSEnTo determine the efficacy of photodynamic therapy (PDT) in the treatment of choroidal metastasis.nnnDESIGNnRetrospective, interventional case series.nnnPARTICIPANTSnNine tumors in 8 eyes of 8 patients.nnnINTERVENTIONnPhotodynamic therapy using verteporfin at a dose of 6 mg/m(2) body surface area and 689 nm diode laser at an intensity of 600 mW/cm(2) for 83 seconds (50 J/cm(2)).nnnMAIN OUTCOME MEASURESnTumor control and best-corrected visual acuity.nnnRESULTSnNine choroidal metastases in 8 eyes were treated with 1 (8 tumors) or 2 (1 tumor) sessions of PDT. The mean tumor basal diameter was 7 mm (median, 7 mm [range, 2-13 mm]), and mean tumor thickness was 2.9 mm (median, 2.9 mm [range, 1.6-4 mm]). All 9 tumors were associated with shallow subretinal fluid. After PDT, complete control with resolution of subretinal fluid was achieved in 7 tumors (78%), with mean tumor thickness reduction of 39% (median, 43% [range, 6%-61%]). Two tumors failed to respond to PDT, both requiring plaque radiotherapy. Improvement or stabilization of vision was achieved in 7 eyes. Photodynamic therapy-related complications included intraretinal hemorrhage in 1 eye.nnnCONCLUSIONSnPhotodynamic therapy can be an effective alternative for the treatment of choroidal metastasis.nnnFINANCIAL DISCLOSURE(S)nThe author(s) have no proprietary or commercial interest in any materials discussed in this article.

Primary canaliculitis: clinical features, microbiological profile, and management outcome.

Purpose: To describe the demographic profile, clinical presentation, microbiological profile, and management outcome of primary canaliculitis. Methods: Single-center, retrospective, interventional case series. Clinical records of all patients diagnosed with primary canaliculitis and treated at the Department of Ophthalmic Plastic Surgery, LV Prasad Eye Institute, Hyderabad, India, between 1987 and 2010 were reviewed. Retrospective data analysis included demographic profile, clinical presentation, microbiological profile, and management outcomes. The management outcome was further analyzed regarding conservative medical treatment alone, versus punctoplasty with canalicular curettage. Results: Of the 74 patients, 40 (54%) were women. Mean age at presentation was 48 years. Right eye was involved in 38 (51%) patients, left eye in 34 (46%) patients, and both eyes in 2 (3%) patients. The mean delay in diagnosis was 10 months. Lower canaliculus was involved in 48 (65%) patients, upper canaliculus in 17 (23%) patients, and both canaliculi in 9 (12%) patients. The most common presenting symptom was epiphora, noted in 63 (85%) patients, and the most common clinical sign was thickening of canalicular portion of eyelid seen in 53 (72%) patients. Microbiological workup was available in 54 patients, of whom 49 (91%) yielded positive results. The most common isolate was staphylococcus species in 19 (39%) patients. Conservative medical therapy (punctal dilatation, canalicular expression, and topical antibiotics) resulted in resolution in 35 of 51 (69%) patients, whereas punctoplasty with canalicular curettage resulted in resolution in all 39 (100%) patients. Of the 74 patients, 57 (70%) resolved completely with single intervention, 14 (19%) with 2 interventions, 6 (8%) with 3 interventions, and 2 (3%) with 4 interventions. Recurrence was noted in 2 (3%) patients that subsequently resolved with treatment. Conclusion: Primary canaliculitis is predominantly a unilateral disease with a significant delay in diagnosis. The microbiological profile of canaliculitis is evolving, with staphylococcus species emerging as the most common pathogen. Although conservative medical therapy is beneficial, punctoplasty with canalicular curettage combined with topical antibiotic therapy is the gold standard treatment for canaliculitis.