Safety and Efficacy of Intravitreal Risuteganib for Non-Exudative AMD: A Multicenter, Phase 2a, Randomized, Clinical Trial.

BACKGROUND AND OBJECTIVE: To evaluate the safety and efficacy of 1.0 mg risuteganib in subjects with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: This was a phase 2a, prospective, double-masked, sham-controlled study. Eyes with nonexudative (dry) AMD and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 20/40 and 20/200 were included. Subjects were randomized to intravitreal 1.0 mg risuteganib or sham injection. At Week 16, subjects in the risuteganib group received a second 1.0-mg dose and the sham group crossed over to receive a dose of 1.0 mg risuteganib and were evaluated at Week 28. The primary endpoint was proportion of subjects with 8 letters ETDRS or more BCVA gain from baseline to Week 28 in the risuteganib group versus baseline to Week 12 for the sham group. BCVA was tested and subjects were observed for adverse events (AEs) every 4 weeks until completion of the study at 32 weeks. RESULTS: Forty-five subjects (risuteganib, n = 29; sham, n = 16) were enrolled in the study, of whom 39 (risuteganib, n = 25; sham, n = 14) completed the study and were included in the per protocol efficacy analysis. At baseline, mean age was 78.8 and 75.9 years and mean BCVA was 67.1 and 64.4 letters in the sham and risuteganib groups, respectively. The primary endpoint was met by 48% of the risuteganib group at Week 28 and 7% of the sham group at Week 12 (P = .013). Of the risuteganib subjects, 20% gained 15 letters or more at Week 28, whereas no patients in the sham group at Week 12 achieved this visual acuity gain. The only ocular treatment-related treatment-emergent AE was vitreous floaters, which spontaneously recovered without sequelae. No drug-related serious AE was reported. CONCLUSIONS: Risuteganib demonstrated significant BCVA improvement in patients with non-exudative AMD. No drug-related AEs were seen during a 32-week observation period. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:327-335.].

Crystalline Maculopathy Secondary to Retinal Tear Without Detachment.

Purpose: Crystalline maculopathy secondary to chronic retinal detachment (RD) has previously been described. This article proposes a novel mechanism to explain crystalline formation in the absence of RD. Methods: Two patients, who were referred for routine examination, were found to have a crystalline maculopathy in the setting of an asymptomatic, chronic-appearing, peripheral retinal tear. Fundoscopy and optical coherence tomography were used to assess the crystals and tear. No specimens were obtained. Results: We describe 2 cases of a crystalline maculopathy secondary to an asymptomatic peripheral retinal tear. We hypothesized macrophage ingestion of photoreceptor segments emanating from the tear may have contributed to macular crystalline deposition. Conclusions: Because crystalline maculopathy can present in the setting of RD, there may be a shared pathogenesis between the 2 conditions.

Retinal pigment epitheliopathy, macular telangiectasis, and intraretinal crystal deposits in HIV-positive patients receiving ritonavir.

PURPOSE: The purpose of this study was to describe the occurrence of a retinal pigment epitheliopathy associated with macular telangiectasis and intraretinal crystal deposits in three human immunodeficiency virus-positive patients receiving long-term ritonavir as part of highly active antiretroviral therapy. METHODS: The patient's records were reviewed. RESULTS: The CD4 T-cell counts at presentation were 163 cells per microliter, 464 cells per microliter, and 349 cells per microliter, and viral loads were undetectable in all patients. None of the patients had a concurrent AIDS-defining illness. Other significant medical history included hyperlipidemia in one patient and a remote history of lymphoma and tuberculosis in a second patient. Initial visual acuity ranged from 20/32 to 20/400, with a median of 20/150. Anterior segment examination and intraocular pressures were normal in all eyes. Posterior segment examination revealed bilateral macular retinal pigment epitheliopathy with intraretinal crystalline deposits. No hemorrhage or cotton wool spots were seen consistent with human immunodeficiency virus retinopathy, and there was no evidence of previous or active cystomegalovirus retinitis. Fluorescein angiography revealed parafoveal telangiectasis with late leakage in two of the three patients. Optical coherence tomography showed thickening of the macula in three eyes and inner foveal cysts in two eyes. Autofluorescence performed on one patient revealed complete loss of normal retinal pigment epithelium autofluorescence corresponding to the area of retinal pigment epitheliopathy bilaterally. The only medicine common to all 3 patients was ritonavir, and the duration of ritonavir therapy before presentation was 19 months in one patient, 30 months in the second patient, and 5 years in the third patient. CONCLUSION: Retinal changes characterized by retinal pigment epitheliopathy, parafoveal telangiectasias, and intraretinal crystal deposits occurred in three human immunodeficiency virus-positive patients on long-term ritonavir as part of highly active antiretroviral therapy.

Obliterative idiopathic juxtafoveolar telangiectasis: a 25-year follow-up.

PURPOSE: To report findings over 25 years of follow-up on a case of bilateral obliterative idiopathic juxtafoveolar retinal telangiectasis. METHOD: Case report. RESULTS: A 25-year-old white man with obliterative idiopathic juxtafoveolar retinal telangiectasis presented with a visual acuity of 20/30 in the right eye and 20/40 in the left. Fluorescein angiography revealed bilateral enlarged foveal avascular zones and late perifoveal leakage. Six years after presentation, the foveal avascular zone had enlarged only slightly in both eyes and the leakage had almost entirely subsided. For the next 19 years, the visual acuity and clinical findings have remained unchanged. His most recent visual acuity was 20/25 in the right eye and 20/40 in the left. No treatment was given throughout the entire follow-up period of 25 years. CONCLUSION: Obliterative idiopathic juxtafoveolar retinal telangiectasis is a rare disorder that may initially progress with subsequent stabilization and good long-term visual outcome.

Angioid streaks and optic nerve head drusen in hyperphosphatemic familial tumoral calcinosis.

PURPOSE: To describe a patient with angioid streaks and optic nerve head drusen associated with familial tumoral calcinosis (FTC). DESIGN: Retrospective, observational case report. METHODS: The patient's records were reviewed. RESULTS: After receiving blunt trauma to the head, the patient presented with loss of vision in the left eye. Fundus examination revealed bilateral angioid streaks, optic nerve head drusen, and choroidal ruptures associated with subretinal hemorrhages. Subsequent physical, laboratory, and radiologic examinations revealed periarticular calcification, elevated serum phosphate levels, and normal calcium levels, consistent with FTC. CONCLUSIONS: FTC should be considered in the differential diagnosis for patients presenting with angioid streaks and optic nerve head drusen.

Resolution of a giant pigment epithelial detachment after treatment with intravitreal bevacizumab.

PURPOSE: To describe a patient with a giant pigment epithelial detachment (PED) successfully treated with intravitreal bevacizumab. DESIGN: Retrospective, observational case report. METHODS: The patient's records were reviewed. RESULTS: An 81-year-old man with history of age-related macular degeneration was seen on routine follow-up examination with an asymptomatic PED temporal to the macula in the right eye and visual acuity of 20/40. The patient was observed. Ten months later, the patient was found to have decreased vision to 20/80 and massive enlargement of the PED, with extension from the temporal equator into the macula. Optical coherence tomography of the macula showed a PED with overlying intraretinal cysts. The patient was given injections of intravitreal bevacizumab for every 4 months (1.25 mg) with complete resolution of the PED and return to baseline visual acuity of 20/40. CONCLUSION: Giant PED secondary to exudative age-related macular degeneration can be successfully treated with intravitreal bevacizumab.

The value-based medicine comparative effectiveness and cost-effectiveness of penetrating keratoplasty for keratoconus.

OBJECTIVE: To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. METHODS: Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). RESULTS: Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. CONCLUSIONS: Penetrating keratoplasty for patients with severe keratoconus seems to be a comparatively effective and cost-effective procedure when compared with other interventions across different medical specialties.

Oculoleptomeningeal amyloidosis in a patient with a TTR Val30Gly mutation in the transthyretin gene.

OBJECTIVE: To describe a patient with oculoleptomeningeal amyloidosis associated with infiltration of the vitreous, elevated intraocular pressures (IOPs), and seizures caused by a TTR Val30Gly mutation in the transthyretin gene. DESIGN: Interventional clinicopathologic report. PARTICIPANT: A 44-year-old man with refractory bilateral intermediate uveitis, elevated IOPs, and seizures. INTERVENTION: The patient underwent diagnostic pars plana vitrectomy in both eyes. Intraocular and intracerebral pressures were controlled by trabeculectomy and cerebroventricular shunt placement, respectively. MAIN OUTCOME MEASURES: Visual acuity, histopathologic analysis of vitreous and leptomeningeal tissue, genetic testing, and magnetic resonance imaging of the brain. RESULTS: After failure of the patient to respond to topical and periocular corticosteroid therapy, a pars plana vitrectomy was performed and revealed amorphous material that showed green birefringence and dichroism on Congo red staining, establishing the diagnosis of vitreous amyloidosis. A full medical workup, including genetic testing, revealed a TTR Val30Gly mutation in the transthyretin gene. The patient subsequently developed elevated IOPs requiring bilateral trabeculectomy surgery and episodic seizures associated with leptomeningeal enhancement on magnetic resonance imaging. Histopathological analysis of a leptomeningeal biopsy taken at the time of surgery revealed amyloid infiltration, confirming the diagnosis of oculoleptomeningeal involvement by his amyloidosis. A ventriculoperitoneal shunt was placed. CONCLUSION: Amyloidosis should be considered in patients who present with vitritis that is unresponsive to corticosteroid therapy. Vitreous biopsy with histopathological analysis is recommended in these cases. Additionally, sequencing of the transthyretin gene should be considered in patients with vitreous amyloidosis to help establish known genetic syndromes and predict both ocular and systemic comorbidities. Although not described previously, elevated IOP may develop in patients with vitreous amyloidosis due to a TTR Val30Gly mutation in the transthyretin gene.

Whole-body positron emission tomography/computed tomography imaging and staging of orbital lymphoma.

OBJECTIVES: To report the use of whole-body positron emission tomography fused with computed tomography (PET/CT) for the diagnosis and staging of orbital lymphoma. DESIGN: Retrospective observational case series. PARTICIPANTS: Four patients with biopsy-proven orbital lymphoma were evaluated by 18-fluoro-2-deoxyglucose whole-body PET/CT imaging. METHODS: Positron emission tomography/CT images were studied for the presence of glucose uptake. Foci were considered suspicious based on their standardized uptake values (SUVs). Physiologic images (PET) and their anatomic counterparts (CT) were fused to allow form and function to be evaluated on the same diagnostic page. MAIN OUTCOME MEASURES: Positron emission tomography/CT images were assessed for foci with abnormally high SUVs that correlated with biopsy-proven lymphoma. RESULTS: Positron emission tomography/CT detected orbital lymphoma in 3 patients (75%). It also revealed systemic lymphoma in 2 of the 4 patients. The 2 patients found to have systemic lymphoma were diagnosed to have extranodal marginal zone B-cell orbital lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Similarly, the 2 with negative PET/CT results also had orbital MALT-type lymphoma. We found that PET/CT imaging helped guide further management in all 4 patients. CONCLUSIONS: Positron emission tomography/CT should be considered as a new method of diagnosing, staging, and restaging patients with orbital lymphomas.