Occlusive Vasculitis Following Intravitreal Rituximab Injection for Primary Vitreoretinal Lymphoma.

PURPOSE: We report three cases of occlusive vasculitis following intravitreal rituximab therapy for biopsy-proven primary vitreoretinal lymphoma (PVRL), one of which was following an injection of the biosimilar Riabni (rituximab-arrx, AmGen) and two of which were following an injection of Rituxan (rituximab, Genentech). METHODS: Case series. RESULTS: Three cases of occlusive vasculitis confirmed with fluorescein angiography are reported 5 days, 8 days, and 3.5 weeks following intravitreal injection of rituximab. The initial vision was poor (20/500, 20/150, and light perception), but vision recovered to baseline in two cases, and remained poor in the case of combined artery and vein occlusion. CONCLUSION: Occlusive vasculitis is a rarely reported but potential complication of intravitreal rituximab therapy in patients who have been previously treated with the agent and may have delayed onset. A low threshold for fluorescein angiography as a diagnostic test for post-injection vision loss and prompt treatment with topical and/or oral steroids should be considered.

Oral HIF-2α Inhibitor Belzutifan in Ocular von Hippel-Lindau Disease: Subgroup Analysis of the Single-Arm Phase 2 LITESPARK-004 Study.

OBJECTIVE: To report the efficacy of oral HIF-2α inhibitor belzutifan in participants with von Hippel-Lindau disease-associated retinal hemangioblastomas in LITESPARK-004. DESIGN: Subgroup analysis of the phase 2, single-arm, open-label LITESPARK-004 study. PARTICIPANTS: Adults with ≥1 von Hippel-Lindau disease-associated measurable renal cell carcinoma tumor not requiring immediate surgical intervention were eligible. METHODS AND INTERVENTION: Participants received oral belzutifan 120 mg once daily until disease progression or unacceptable treatment-related toxicity. MAIN OUTCOME MEASURES: Efficacy of belzutifan in retinal hemangioblastomas was a secondary end point, measured as response (improved, stable, or progressed) by independent reading center certified graders based on color fundus imaging performed every 12 weeks using the investigator's preferred imaging standards. Additional assessments, where available, included optical coherence tomography and ultra-widefield fluorescein angiography. RESULTS: Among 61 participants in LITESPARK-004, 12 had ≥1 evaluable active retinal hemangioblastoma in 16 eyes at baseline per independent reading center. As of April 1, 2022, the median follow-up for participants with ocular von Hippel-Lindau disease at baseline was 37.3 months. All 16 eyes were graded as improved, with a response rate of 100.0% (95% confidence intervals, 79.4-100.0). No new retinal hemangioblastomas or ocular disease progression were reported as of data cutoff date. Eight participants had additional multimodal eye assessments performed at the National Institutes of Health study site. Among this subgroup, 10 of 24 hemangioblastomas in 8 eyes of 6 participants measured ≥500 µm in greatest linear dimension at baseline and were further analyzed. All 10 hemangioblastomas had a mean area reduction of ≥15% by month 12 and ≥30% by month 24. CONCLUSIONS: Belzutifan showed promising activity against ocular von Hippel-Lindau disease, including capacity to control retinal hemangioblastomas, with effects sustained for >2 years while on treatment.

Posterior Uveitis in Ocular-Involving Chronic Lymphocytic Leukemia and the Utility of Negative MYD88 L265P Testing in the Diagnosis.

Introduction: The aim of this study was to investigate if a negative test result for MYD88 L265P mutation, associated with vitreoretinal lymphoma (VRL) and primary CNS lymphoma, in liquid biopsies from intraocular fluids can be a useful adjuvant test to diagnose chronic lymphocytic leukemia in clinically challenging cases. Case Presentations: We selected patients with a past medical history or examinations findings suspicious for intraocular lymphoma. We evaluated both vitreous and aqueous humor-derived (AHD) MYD88 L265P mutation from patients that had suspected intraocular lymphoma that warranted a liquid biopsy procedure. Gold-standard cytopathology, flow cytometry, and gene rearrangement studies were also performed. All 4 patients had negative AHD MYD88 L265P mutation testing. Gold-standard testing (cytology) either showed paucicellular specimens (1/4) or specimens with high background inflammation (3/4). One case showed a rare B-cell clonal population (CD5+, Kappa-restricted by flow cytometry), but this was not sufficient to make any definitive diagnosis. All patients were subsequently initiated on systemic therapy and had improvement in their disease burden. Conclusions: Negative AHD MYD88 L265P mutation testing can serve as an adjuvant molecular test to diagnose difficult cases of intraocular CLL.

Conjunctival Apocrine Hidrocystoma: A Case Report and Review of Literature.

PURPOSE: To describe the clinical features of a conjunctival apocrine hidrocystoma that developed 6 decades after a strabismus surgery and review existing literature on apocrine hidrocystomas of the conjunctiva and caruncle. METHODS: Case report and review of literature on conjunctival apocrine hidrocystomas. RESULTS: A 71-year-old man with a history of strabismus surgery as a child presented with a cystic lesion on the nasal conjunctiva and caruncle for 1 year. Excision of the lesion showed a unilocular cavity lined by a double layer of cells with the hallmark finding of apical decapitations, confirming a diagnosis of apocrine hidrocystoma. Seven additional cases of conjunctival and caruncular apocrine hidrocystomas were reviewed. All cases presented after 50 year of age. Most cases presented nasally or within the caruncle and had a pigmented appearance. No other reported cases had a history of trauma or surgery. All cases were treated with surgical excision without recurrence. CONCLUSIONS: History of strabismus surgery or conjunctival trauma may lead to ectopic deposition of apocrine glands that may contribute to the formation of an apocrine hidrocystoma.

Immunotherapy for a Choroidal Pigmented Lesion.

A 51-year-old male with a a history of BRAF V600 E mutation-positive, superficial spreading-type cutaneous melanoma on the chest with metastasis to a sentinel lymph node had a 4-week history of redness and swelling of the right temporal bulbar conjunctiva and was referred for evaluation of a choroidal lesion in the right eye. What would you do next?

Targeted therapy in ophthalmic oncology: The current status.

There have been rapid advancements in the field of ocular oncology for the diagnosis and management of intraocular, adnexal, and orbital tumors. Targeted therapy is in the forefront of medical research in all fields including ocular oncology. Targeted therapy include drugs that target specific genetic mutations, pathways or proteins involved in the development of cancer. In contrast to traditionally used chemotherapy, drugs used in targeted therapy are highly specific for tumor cells and preserve the function of normal cells. This review aims to familiarize ophthalmologists with the drugs that are currently approved or undergoing clinical trials for use in ocular oncology. Targeted therapy is particularly useful for locally advanced or metastatic tumors, including but not limited to eyelid and periocular basal cell carcinoma, periocular cutaneous and conjunctival squamous cell carcinoma, ocular adnexal lymphoma, conjunctival melanoma, and uveal melanoma. The results are promising with improved survival outcomes and better tolerability than chemotherapeutic drugs.

Relationships between internet addiction, smartphone addiction, sleep quality, and academic performance among high-school students.

OBJECTIVE: In this study, we aimed to evaluate the relationships between Internet addiction, smartphone addiction, sleep quality, and academic success. METHODS: In this cross-sectional study, high-school students were surveyed to evaluate sleep quality, Internet addiction, and smartphone addiction. Students were queried about their demographics, and grade averages from the previous term were taken as an indicator of academic success. RESULTS: A total of 1,959 students were enrolled in this study, with 1,034 (52.8%) girls and 925 (47.2%) boys, and the median age of the participants was 16 (13-21) years. Multivariate analyses found that poor sleep quality in students who did not have breakfast before going to school was 1.58 times higher than those who did (p<0.001). Students who stayed in a dormitory had 1.79 times more poor sleep quality than those who stayed with their family, and a one-unit increase in the total score of the Young's Internet Addiction Test short form resulted in a 1.08-fold increase (both, p<0.001). CONCLUSION: Our study has shown that students' sleep quality was predicted to be lower if they stayed in a dormitory and skipped breakfast. In addition, Internet and smartphone addictions have a negative effect on sleep quality and academic performance.

Multispecialty Management of Metastatic Colon Adenocarcinoma Involving the Extraocular Muscles: Primary Excision and Simultaneous Treatment of Strabismus With a Review of the Literature.

Metastatic colon adenocarcinoma involving the extraocular muscles is extremely rare. It usually develops following the diagnosis of the systemic disease and therefore, management and treatment require a multispecialty approach. Within this manuscript, we provide a summary of cases of orbital metastasis secondary to colon cancer. We further discuss a detailed case of a 42-year-old male patient who developed recent-onset diplopia in the left gaze. Orbital CT imaging showed a localized, well-circumscribed enlargement of the right medial rectus muscle. The biopsy of the right medial rectus showed adenocarcinoma originating from the gastrointestinal system. Further workup revealed colon adenocarcinoma with multiple metastatic sites. The patient started systemic chemotherapy. After 2 months of chemotherapy (5-fluouracil, oxaliplatin, irinotecan, and leucovorin), all systemic metastatic sites regressed; however, his medial rectus muscle continued to grow, causing compressive optic neuropathy. The patient underwent excisional biopsy of the right medial rectus muscle with simultaneous repair of the strabismus with transposition of superior and inferior recti muscles. He continued with systemic chemotherapy. Follow up in 1 year revealed no local orbital tumor recurrence with excellent visual acuity and no diplopia in primary gaze.

SUPRACHOROIDAL SPACE INJECTION TECHNIQUE: Expert Panel Guidance.

PURPOSE: To develop professional guidelines for best practices for suprachoroidal space (SCS) injection, an innovative technique for retinal therapeutic delivery, based on current published evidence and clinical experience. METHODS: A panel of expert ophthalmologists reviewed current published evidence and clinical experience during a live working group meeting to define points of consensus and key clinical considerations to inform the development of guidelines for in-office SCS injection. RESULTS: Core consensus guidelines for in-office SCS injection were reached and reported by the expert panel. Current clinical evidence and physician experience supported SCS injection as a safe and effective method for delivering retinal and choroidal therapeutics. The panel established consensus on the rationale for SCS injection, including potential benefits relative to other intraocular delivery methods and current best practices in patient preparation, pre- and peri-injection management, SCS-specific injection techniques, and postinjection management and follow-up. CONCLUSION: These expert panel guidelines may support and promote standardization of SCS injection technique, with the goal of optimizing patient safety and outcomes. Some aspects of the procedure may reasonably be modified based on the clinical setting and physician judgment, as well as additional study.

Bilateral Choroidal Detachments Associated with Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) - Associated Vasculitis.

PURPOSE: To report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases. METHODS: Case report. RESULTS: A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments. CONCLUSION: Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis.

Use of Cemiplimab, an Immune Checkpoint Inhibitor for Conjunctival Intraepithelial Neoplasia.

PURPOSE: Immune checkpoint inhibitors (ICIs) have been recently introduced for the treatment of locally unresectable conjunctival squamous cell carcinoma. We present 2 cases with conjunctival intraepithelial neoplasia (CIN) who were treated with ICIs. METHODS: A report of 2 cases with CIN who were treated with systemic cemiplimab (350 mg IV every 3 weeks). RESULTS: A 70-year-old man was treated with cemiplimab for metastatic cutaneous squamous cell carcinoma. The pre-existing CIN continued to progress over the nasal bulbar conjunctiva and cornea, while the other metastatic sites, including parotid glands, and neck lymph nodes showed a complete response after 16 cycles of treatment. An 84-year-old woman had bilateral diffuse CIN involving bulbar and lower eyelid palpebral conjunctiva. Cemiplimab was started because of the extent of involvement. While the bulk of CIN was reduced, it progressed over the cornea and forniceal conjunctiva on OU after 10 cycles of treatment. Excisional biopsies of conjunctival lesions after cemiplimab confirmed CIN in both patients. CONCLUSIONS: Although conjunctival squamous cell carcinoma tumors are reported to be highly responsive to ICIs, a similar effect has not been observed in 2 patients with CIN. Further studies are needed to evaluate ICIs in the management of CIN.

Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review.

PURPOSE: To review the outcomes of targeted therapy and immunotherapy in advanced conjunctival tumors, including conjunctival squamous cell carcinoma, conjunctival melanoma, and conjunctival lymphoma. METHODS: A Pubmed database systematic search was performed between January 1999 and December 2022. The literature search was limited to studies published in English. RESULTS: This review included 142 patients with advanced malignant conjunctival tumors from 42 articles. In the conjunctival squamous cell carcinoma group, 2 cases of advanced conjunctival squamous cell carcinoma treated with epidermal growth factor receptor inhibitors showed significant tumor size improvement after 7.5 months of follow-up. Among 7 cases treated with systemic immunotherapy, 5 cases (72%) had complete response (CR), 1 case (14%) showed partial response (PR), and 1 case (14%) had stable disease (SD) after 16 months. In the conjunctival melanoma group, among 18 cases treated with combined v-raf murine sarcoma viral oncogene homolog B1/mitogen-activated extracellular signal-regulated kinase inhibitors, 6 (33%) had CR, 5 (28%) had PR, 2 (11%) had SD, and 5 (28%) had progressive disease after 24.8 months of follow-up. Of 44 conjunctival melanoma cases treated with immunotherapy, 12 (28%) had CR, 9 (20%) had PR, 7(16%) had SD, and 16 (36%) had progressive disease after 14.2 months. Systemic Rituximab treatment for conjunctival lymphoma cases resulted in CR in 21 patients (63%), PR in 11 patients (33%), and SD in 1 patient (3%) after 20.5 months of follow-up. Intralesional Rituximab injections in 38 conjunctival lymphoma cases showed CR in 28 patients (75%), PR in 7 patients (19%), SD in 1 patient (2%), and progressive disease in 2 patients (4%) after 20.4 months of follow-up. CONCLUSIONS: Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Review of Targeted Therapy, Vismodegib, for the Treatment of Periocular Basal Cell Carcinoma.

PURPOSE: Periocular locally advanced basal cell carcinoma (POLA-BCC) is characterized by orbital involvement and/or extensive invasion of periocular structures. Hedgehog pathway inhibitors have been used for POLA-BCC with promising outcomes. METHODS: The authors reviewed 11 articles published in English literature from January 2012 to July 2022 and reported the outcomes of patients with POLA-BCC who were treated with vismodegib. RESULTS: A total of 384 patients were treated with vismodegib. The mean age was 72 years, and the median treatment duration was 9 months. The overall response rate was 75% with a median follow-up time of 14.4 months. Following vismodegib treatment, the median number of patients who required adjuvant surgery was 43% with a median time to surgery of 6.5 months. The exenteration rate was 6% (overall 8 patients). In total 93.7% of patients experienced grade I adverse events, 26.7% to 37.5% grade II, 8.8% to 10% grade III-IV, and 0.8% to 4.8% grade V. Major side effects included dysgeusia (30-100%), muscle spasm (15-100%), alopecia (47-75%), weight loss (23-83%), and decreased appetite (19-42%). The median percentage of patients who discontinued treatment due to toxicity was 29% with a median interval of 5 months before the development of side effects. The median recurrence rate following discontinuation of vismodegib was 7.8% with a median recurrence duration of 20 months. CONCLUSIONS: In patients with POLA-BCC, vismodegib, a hedgehog pathway inhibitor, provided high rates of orbital preservation, reducing exenteration rates to 6%. Neoadjuvant therapy with vismodegib can also be suggested for patients with POLA-BCC. While extremely effective, side effects lead to temporary or permanent discontinuation of vismodegib in small numbers of patients.

INTRAVITREAL MELPHALAN INJECTION AS A SECOND-LINE LOCAL THERAPY IN VITREORETINAL LYMPHOMA: Case Series.

PURPOSE: To evaluate the effectiveness and safety of intravitreal melphalan (IVM) injection therapy in vitreoretinal lymphoma. METHODS: Eight eyes of five biopsy-proven vitreoretinal lymphoma patients who were treated with IVM injection as a second-line therapy after intravitreal methotrexate and rituximab injections were retrospectively evaluated between January 2011 and March 2023. RESULTS: The medical records of five vitreoretinal lymphoma patients (mean age of 62 years at the diagnosis) including 4 (80%) female patients and 1 (20%) male patient were retrospectively analyzed. Three patients (60%) either had a history of central nervous lymphoma or developed it during the follow-up. Patients were previously treated with a mean of five cycles of monthly intravitreal methotrexate and rituximab injections. All eyes showed complete response by the disappearance of vitreal and/or subretinal neoplastic cells within 6 weeks after IVM injections (range, 1-4 injections per eye). Of 12 IVM injections, 3 (25%) injections were associated with macular edema diagnosed on optical coherence tomography at 1-month follow-up and resolved spontaneously within 5 months. The IVM administration induced new retinal pigment epithelium changes in three eyes (37%). CONCLUSION: Intravitreal melphalan injection may be effective in the management of vitreoretinal lymphoma as a second-line local therapy. Randomized clinical trials with larger numbers of patients are needed to establish the efficacy, treatment protocol, and safety of IVM injection.

Relationships between internet addiction, smartphone addiction, sleep quality, and academic performance among high-school students

SUMMARY OBJECTIVE: In this study, we aimed to evaluate the relationships between Internet addiction, smartphone addiction, sleep quality, and academic success. METHODS: In this cross-sectional study, high-school students were surveyed to evaluate sleep quality, Internet addiction, and smartphone addiction. Students were queried about their demographics, and grade averages from the previous term were taken as an indicator of academic success. RESULTS: A total of 1,959 students were enrolled in this study, with 1,034 (52.8%) girls and 925 (47.2%) boys, and the median age of the participants was 16 (13-21) years. Multivariate analyses found that poor sleep quality in students who did not have breakfast before going to school was 1.58 times higher than those who did (p<0.001). Students who stayed in a dormitory had 1.79 times more poor sleep quality than those who stayed with their family, and a one-unit increase in the total score of the Young's Internet Addiction Test short form resulted in a 1.08-fold increase (both, p<0.001). CONCLUSION: Our study has shown that students' sleep quality was predicted to be lower if they stayed in a dormitory and skipped breakfast. In addition, Internet and smartphone addictions have a negative effect on sleep quality and academic performance.

Orbital biopsy findings consistent with granulomatosis polyangiitis in a 14-year-old boy with Crohn's disease.

Both granulomatous polyangiitis (GPA) and Crohn's disease (CD) can cause orbital inflammation though rarely coincide and can often be differentiated by presenting features and histological findings. Here, we report the clinical and therapeutic course of a 14-year-old White male with binocular diplopia caused by orbital myositis. Imaging and biopsy obtained at presentation revealed necrosis and necrotizing granulomatous vasculitis suspicious for GPA. He subsequently developed gastrointestinal symptoms and terminal ileitis consistent with CD. Orbital symptoms responded well to high-dose steroids and remained quiet on methotrexate maintenance therapy. While clinical history, thorough physical exam, and complete laboratory work-up are essential in the management of pediatric orbital myositis, orbital biopsy can prove critical for diagnosis and suitable treatment strategy.

Intralesional or intraorbital rituximab injection for the management of biopsy-proven idiopathic orbital inflammation involving the lacrimal gland.

OBJECTIVE: To evaluate the efficacy of intralesional rituximab injection for the management of idiopathic orbital inflammation (IOI) involving the lacrimal gland, which is the most common subtype. METHOD: Eighteen consecutive patients with biopsy-proven IOI involving the lacrimal gland were included. Rituximab (50 mg/5 mL) was injected intralesionally at monthly intervals. RESULTS: Clinically, all patients presented with upper eyelid swelling and ptosis. Most patients (56%) had periocular pain and a palpable superotemporal mass. Biopsies showed chronic inflammation without fibrosis in 14 patients (78%) and chronic inflammation and fibrosis in 4 patients (22%). Intralesional rituximab was injected once in 1 patient (6%) because of complete response after the first injection, twice in 11 patients (61%), and 3 times in 6 patients (33%) because of partial response after 2 injections. After a mean follow-up of 33 months (median, 33 months; range, 11-59 months), 16 patients (89%) showed a clinical response, including 14 patients (78%) a complete response (i.e., disappearance of all lesions) and 2 patients (11%) with a partial response (i.e., ≤30% decrease in lesion diameter). Two patients (11%) did not respond after 3 injections and were placed on systemic corticosteroid and methotrexate therapies. Two patients (11%) with a complete response developed subsequent recurrence 12 and 49 months after their last injections. Both were treated with 2 additional rituximab injections, 1 month apart, and showed complete response when examined 27 and 11 months after treatment, respectively. CONCLUSION: Intralesional rituximab injection may be an effective treatment for IOI involving the lacrimal gland, achieving a 78% complete response rate in this series. Local treatment with rituximab has the potential to avoid the ocular and systemic side effects of corticosteroid and systemic immunosuppressive treatment.

Scleral ectasia stabilization following intra-arterial chemotherapy in an eye with recurrent retinoblastoma.

Purpose: To report a case of recurrent retinoblastoma following transpupillary thermotherapy (TTT) with development of scleral ectasia, as well as their successful treatment with intra-arterial chemotherapy. Observations: A 15-month-old girl with bilateral retinoblastoma presented with recurrent retinoblastoma and associated scleral ectasia with concern for extraocular extension after receiving multiple round of systemic chemotherapy and TTT. Given her negative systemic evaluation, decision was made to pursue intra-arterial chemotherapy. After completion of six rounds of 3-agent intra-arterial chemotherapy, the recurrent retinoblastoma had completely regressed and the scleral ectasia had improved and fibrosed. Conclusions and importance: The sclera is classically viewed as hyperthermy-resistant to TTT. Here, we describe scleral ectasia due to aggressive TTT with recurrence of the retinoblastoma. Our treatment with intra-arterial chemotherapy not only caused complete regression of the recurrent retinoblastoma, but it also contributed to the stabilization and improvement of the weakened scleral.