Ciliary Madarosis Secondary to Intra-Arterial Chemotherapy for Retinoblastoma Treatment.

Background: Retinoblastoma is the most common intraocular tumor in the pediatric population. Its main therapeutic objectives are to avoid fatal outcomes and preserve vision as much as possible. Intra-arterial chemotherapy (IAC) improves drug delivery and reduces possible systemic adverse effects. This modality allows direct administration of chemotherapeutic agents to intraocular malignancies via the ophthalmic artery (OA), proving to be a feasible and effective method for globe salvage. Most side effects of IAC are local, including eyelash loss of the nasal portion of the eyelid. Summary: We performed a comprehensive review to analyze data regarding ciliary madarosis in patients diagnosed with retinoblastoma treated with IAC. We describe 9 studies with a total of 637 eyes with retinoblastoma that underwent IAC, of which 45 cases presented madarosis. In chemotherapy-induced alopecia, there is hair shaft thinning and breakage. On trichoscopy, the remaining end of the fractured hair will be observed as black dots. Differential diagnoses must include alopecia areata and trichotillomania. Key Messages: Ciliary madarosis secondary to IAC, although transitional, may cause discomfort in patients and family members. Physical examination, as well as a trichoscopic evaluation of the affected area, can help in reaching a prompt diagnosis and prognosis for this particular alopecia.

Leukemic infiltration of the ciliary body in a child with T-cell acute lymphoblastic leukemia.

A 14-year-old boy presented after 2 months of vision loss, redness, and pain in the right eye, initially treated as anterior uveitis with topical corticosteroids. He had a 1-year history of T-cell acute lymphoblastic leukemia, which had been in remission for 6 months. On examination, visual acuity in the right eye was light perception, with 4+ anterior chamber cells, pupillary membrane, and an intumescent cataract. Ultrasound biomicroscopy (UBM) revealed a ciliary body mass and capsular bag rupture. After consultation with his oncologist, he received 10 radiotherapy sessions. At 1 month, UBM showed resolution of the mass. After 1 year of remission, the patient underwent pars plana vitrectomy, pupillary membranectomy, and placement of a scleral-fixated intraocular lens. Thirty months after surgery, visual acuity was 20/25. Leukemic infiltration of the ciliary body is a rare manifestation of the disease that is often misdiagnosed as uveitis.

Retinal Ischemia Following Focal Cerebral Arteriopathy in a Young Girl.

PURPOSE: We present a case of an ischemic retinopathy with severe vision loss secondary to a childhood stroke. METHODS: Case report. RESULTS: An otherwise healthy 9-year-old girl presented with a 1-day history of impaired gait and speech. After performing Computed Tomography and Magnetic Resonance Imaging, thrombosis of the left Internal Carotid Artery was observed and a diagnosis of ischemic stroke was established. Serological autoimmune, coagulation, and viral panels were unrewarding. Cardiac, inflammatory and coagulation disorders were ruled out. The cause was attributed to a Focal Cerebral Arteriopathy, a common cause of childhood stroke. The patient was treated with mechanical thrombectomy followed by anticoagulation. The day after, the patient referred vision loss of 20/100 in the left eye. Fundus evaluation of the left eye depicted diffuse intraretinal hemorrhages as well as cotton-wool spots and there was retinal whitening at the posterior pole. Six weeks after, visual acuity dropped to counting fingers. CONCLUSIONS: A macular optical coherence tomography revealed diffuse atrophic changes in the inner retinal layers at the macula, and the Angio-OCT showed an enlarged Foveal Avascular Zone. We propose ischemia-reperfusion as the primary explanation of this unusual event.

Beneath the surface: a case report of metastatic iridociliary ring melanoma treated with pembrolizumab / Abaixo da superfície: relato de caso de melanoma metastático iridociliar em anel tratado com pembrolizumabe

ABSTRACT Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.

RESUMO O melanoma iridociliar em anel é um tipo incomum de melanoma uveal. As manifestações clínicas variam desde casos assintomáticos até síndromes mascaradas que mimetizam um glaucoma refratário. As opções de tratamento incluem radioterapia e enucleação. O manejo do melanoma uveal metastático continua desanimador. Novas terapias usando inibidores de checkpoint imunológico estão atualmente em estudo. Apresentamos o caso de uma mulher hispânica de 54 anos com perda progressiva da visão por um melanoma metastático em anel, com semeadura de câmara anterior, tratada com pembrolizumabe.

Novel RB1 germline mutation in a healthy man.

BACKGROUND: Retinoblastoma (Rb) most frequently presents as a unilateral sporadic disease up to 40% of cases, however, arise from a monoallelic germline pathogenic variant. Only 10% of the germline mutations are inherited, and high penetrance is seen in up to 90% of these cases. As an effort to optimize counseling and screening, mutations are classified according to inheritance patterns. However, RB1 spectrum is highly heterogeneous, and information for unaffected carriers remains scarce. MATERIALS AND METHODS: The Mexican family of a 5-month-old patient diagnosed with Rb was studied. The family consisted of five individuals (father, mother, and three siblings). Genetic testing using a next-generation sequencing assay targeting RB1 with oligonucleotide baits designed to capture its exons and 20 bases flanking intronic sequences was performed in every family member. Clinical history and a complete ophthalmological examination (best-corrected visual acuity, slit-lamp biomicroscopy, macular optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and electrophysiological studies) were performed in members testing positive to RB1 mutation. RESULTS: The father and her five-month-old daughter tested positive for a non-synonymous RB1 mutation c.459del (p.Lys154Serfs*21). The girl presented with bilateral retinoblastoma, successfully treated with cryotherapy and intravenous chemotherapy. The father had no relevant findings on imaging studies or ophthalmologic evaluation. CONCLUSIONS: This report describes a rare case of a novel low-penetrance RB1 germline mutation. Long-term follow-up of the father will include periodic evaluation of the eyes and orbits, and surveillance for systemic sarcoma and secondary malignancies. Implications for unaffected individuals need to be further studied.

Beneath the surface: a case report of metastatic iridociliary ring melanoma treated with pembrolizumab.

Iridociliary ring melanoma is an uncommon type of uveal melanoma. Clinical manifestation varies from asymptomatic cases to masquerade syndromes mimicking refractory glaucoma. Treatment options include radiotherapy and enucleation. Management of metastatic uveal melanoma remains discouraging. Novel therapies using immune checkpoint inhibitors are currently under study. We present a case of a 54-year-old Hispanic woman with progressive vision loss due to metastatic ring melanoma with anterior chamber seeding treated with pembrolizumab.

Retinoblastoma in an older Hispanic child masquerading as pars planitis: A case report.

INTRODUCTION: To report a case of a Hispanic girl with late-onset Retinoblastoma (Rb) who was misdiagnosed as a pars planitis prior to referral. Nearly 95% of all Rb cases are detected before age 5, and this patient was 8 years-old. METHODS: Case report of a late-onset Retinoblastoma with anterior chamber (AC) involvement plus the presence of an Ahmed valve. The patient had a history of a couple of months of topical therapy comprising medication for glaucoma, systemic steroids, and a filtration surgery (Ahmed valve), after that a biopsy was performed prior to referral. Upon arrival at our clinic, we performed an examination under anesthesia (EUA) and a B-scan ultrasound (US). RESULTS: Unilateral Retinoblastoma with an Ahmed valve in an AC filled with Rb seeds was diagnosed with the EUA and US in the left eye. An orbital exenteration with map biopsies of the left orbital cavity was performed with confirmation by histopathology of a poorly differentiated endophytic retinoblastoma with Bruch's membrane invasion. Follow-up sessions were then arranged as well as subsequent systemic chemotherapy cycles. CONCLUSION: Given the rare incidence of retinoblastoma in children older than 5 years old, it can be easily mistaken for other differential diagnoses and treated with filtration surgeries that could put the patient's life at risk. In this report, late-onset Rb diagnosis is highlighted as a differential diagnosis in children and adults with atypical uveitis, which required a multidisciplinary approach.

ASSOCIATION OF VITREORETINAL LYMPHOMA WITH SYSTEMIC LYMPHOMA.

PURPOSE: To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL). METHODS: Single-center retrospective review of medical records. RESULTS: Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate. CONCLUSION: We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.

UNRAVELED FRINGE-LIKE MARGINS AND BIPHASIC AUTOFLUORESCENCE OF UNILATERAL RETINAL PIGMENT EPITHELIUM DYSGENESIS.

PURPOSE: To illustrate the features of unilateral retinal pigment epithelium dysgenesis (URPED) in an African-American male patient. METHODS: Case report. RESULTS: A 47-year-old asymptomatic African-American man was referred for an atypical subretinal pigmented mass in the left eye. On examination, visual acuity was 20/20 in both eyes. The right eye was unremarkable. The left eye revealed a darkly pigmented grey-black lesion at the level of the RPE with irregular, unraveled fringe-like margins, consistent with URPED. The lesion measured 5 mm in basal dimension and was located 400 µm from the foveola. The dark portion of the lesion was grey-black and demonstrated homogeneous hypoautofluorescence, particularly at the site of grey-white peripheral fringe of fibrous metaplasia. By contrast, there was an additional, subtle lacey arrangement of normal-appearing RPE traversing over the entire lesion demonstrating isoautofluorescence. On fluorescein angiography, the lesion was generally hypofluorescent, particularly in the dark portion of the lesion, but the peripheral fringe of fibrous metaplasia displayed angiographic hyperfluorescent staining, and the subtle lacey normal RPE showed isofluorescence. Optical coherence tomography demonstrated RPE hyperplasia and shallow RPE detachment interspersed with normal-appearing RPE and thinning of outer retina and preservation of the foveola and choroid. CONCLUSION: In this case, URPED demonstrated biphasic autofluorescence implying RPE dysfunction in the hypoautofluorescent area and partial RPE function in the lacey isoautofluorescent region.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

PURPOSE: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). METHODS: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. RESULTS: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. CONCLUSION: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

Diffuse infiltrative retinoblastoma with retinal detachment in "cinnamon-roll" configuration: a case report.

A 4-year-old girl presented with leukocoria, vision loss, and painless left eye redness. Posterior segment examination revealed a total retinal detachment and abnormal, tortuous retinal vessels in the left eye. No visible mass, vitreous seeding, or hemorrhage were observed. B-mode ultrasound showed a detached retina in a "cinnamon-roll" configuration. Due to poor visual prognosis and high clinical suspicion of malignancy, enucleation was performed. Further histopathological analysis confirmed the diagnosis of diffuse infiltrative retinoblastoma, with an atypical presentation.

Modern treatment of retinoblastoma: A 2020 review.

Retinoblastoma management remains complex, requiring individualized treatment based on International Classification of Retinoblastoma (ICRB) staging, germline mutation status, family psychosocial factors and cultural beliefs, and available institutional resources. For this 2020 retinoblastoma review, PubMed was searched for articles dated as early as 1931, with an emphasis on articles from 1990 to the present day, using keywords of retinoblastoma, chemotherapy, intravenous chemotherapy, chemoreduction, intra-arterial chemotherapy, ophthalmic artery chemosurgery, intravitreal chemotherapy, intracameral chemotherapy, cryotherapy, transpupillary thermotherapy, laser, radiation, external beam radiotherapy, plaque radiotherapy, brachytherapy, and enucleation. We discuss current treatment modalities as used in the year 2020, including intravenous chemotherapy (IVC), intra-arterial chemotherapy (IAC), intravitreal chemotherapy (IvitC), intracameral chemotherapy (IcamC), consolidation therapies (cryotherapy and transpupillary thermotherapy [TTT]), radiation-based therapies (external beam radiotherapy [EBRT] and plaque radiotherapy), and enucleation. Additionally, we present a consensus treatment algorithm based on the agreement of three North American retinoblastoma treatment centers, and encourage further collaboration amongst the world's most expert retinoblastoma treatment centers in order to develop consensus management plans and continue advancement in the identification and treatment of this childhood cancer.

Challenge of Retinoblastoma in Mexico in 2020: Perspectives and Solutions.

Early diagnosis and positive outcomes of retinoblastoma in childhood have been positively correlated with the economic wealth of high-income countries (HICs) worldwide. Adequate curability and survival rates, adherence to treatment, presence of poor prognostic initial clinical signs, and metastatic disease at diagnosis appear to have a less favorable picture in low-income countries (LICs). However, this is not always the case. An example is Argentina, where disease-free survival rates of retinoblastoma are notably higher than expected when taking into consideration its economic situation. Unfortunately, as in other Latin American LICs, retinoblastoma outcomes in Mexico are worrisome. Interestingly, the Human Development Index (HDI) in Mexico varies widely between its different geographical regions. While in some states, the HDI resembles those of high-income countries, and in others, the opposite is observed. A unifying picture of Mexico's developmental status, health resources, indicators, and other factors possibly influencing outcomes in retinoblastoma is currently unavailable. The present review explores the previously mentioned factors in Mexico and compares them to other countries. Additionally, it recommends solutions or enhancements where possible.

The Use of Alternative Routes for the Delivery of Intra-Arterial Chemotherapy for Retinoblastoma.

BACKGROUND: The introduction of intra-arterial chemotherapy (IAC) for treatment of retinoblastoma considerably changed the paradigm by which this disease is managed, with event-free survival rates being above 70%. OBJECTIVE: To analyze efficacy of IAC treatment using alternative approaches to ophthalmic artery catheterization (OAC), such as external carotid artery approach or balloon-assisted drug delivery. METHODS: This is a retrospective chart review for subjects receiving IAC for retinoblastoma. The primary approach was OAC. In cases in which selective OAC was not feasible, alternative routes including catheterization of the external carotid artery or use of a balloon-assisted drug infusion were used. RESULTS: This study included 197 consecutive patients with 207 retinoblastomas who underwent 658 IAC procedures overall. The mean age at diagnosis was 24 mo, and 54.5% of the study population was male. Success rate with IAC was 97% (639). Alternative approaches to OAC were, in total, 42 cases (6.4%)-external carotid artery catheterization and use of ICA balloon were performed in 22 (3.3%) and 20 (3%) cases, respectively. A mean of 3.1 IAC cycles were performed for each patient. In total, there were 23 technical failures of the primary OAC technique (3.4%). Periprocedural adverse events occurred in 4 procedures (0.6%). Use of an alternative technique for chemotherapy delivery other than selective OAC in at least one IAC cycle was not a predictor of enucleation. CONCLUSION: IAC is a safe and effective treatment option for retinoblastoma. Chemotherapy delivery using alternative techniques is as effective as selective OAC.

Wide-Field (15â€Š× 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

PURPOSE: The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA). DESIGN: Single-centre retrospective review. METHODS: Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA). RESULTS: At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P < 0.001, and 46% vs 48%, P = 0.001, respectively), peripapillary region (66% vs 77%, P < 0.001, and 66% vs 72%, P = 0.001, respectively), and papillomacular bundle (60% vs 68%, P < 0.001, and 61% vs 64%, P = 0.03, respectively). Comparison (no CERR vs controls) revealed nonsignificant foveal avascular zone enlargement (1.20 vs 0.23 mm, P = 0.16) and reduction of CVD in the superficial plexus (46% vs 47%, P = 0.008), and not the deep plexus (48% vs 48%, P = 0.42) of the total wide-field. Comparison of irradiated eyes (CERR vs no CERR) showed reduction of CVD in the superficial and deep plexus of the total wide-field (43% vs 46%, P < 0.006, and 46% vs 48% P < 0.02, respectively), peripapillary region (66% vs 74%, P < 0.001, and 66% vs 72% P < 0.01, respectively), and superficial plexus in the papillomacular bundle (60% vs 65%, P = 0.03). CONCLUSIONS: Following plaque radiotherapy for choroidal melanoma, wide-field swept-source optical coherence tomography angiography demonstrates retinal microvascular abnormalities in the CVD in eyes with and without CERR. These findings are important in early detection and monitoring of radiation retinopathy.