Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial.

BACKGROUND: A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. METHODS: PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). FINDINGS: Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). INTERPRETATION: Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. FUNDING: Regeneron Pharmaceuticals and Bayer.

Spontaneous macular hole closure in bilateral macular holes.

The natural course of full thickness macular hole is progression in size and stage. There have been reports of spontaneous closure of unilateral idiopathic full thickness macular holes, but we report the first case of spontaneous closure of a full thickness macular hole in one eye in a patient with bilateral idiopathic full thickness macular holes. After macular hole surgery in the left eye of the patient, spontaneous closure of the macular hole in the right eye was observed during the follow-up period.

Syphilitic scleritis and choroidal malignant melanoma of the same eye.

A 42-year-old Italian homosexual presented with a red painful eye associated with exudative retinal detachment that was subsequently attributed to syphilitic posterior scleritis. These findings all resolved with intravenous penicillin therapy. However, choroidal mass lesion persisted and subsequent ancillary imaging including B scan and ultrasonography confirmed the presence of a choroidal melanoma, which was treated with radioactive plaque therapy. This case report will describe the interesting findings of this unique presentation.

Optos Panoramic200A fluorescein angiography for proliferative diabetic retinopathy with asteroid hyalosis.

We report a unique situation in which the use of Optos Panoramic200A fluorescein angiography directed the management of a patient with asteroid hyalosis and active proliferative diabetic retinopathy. The Optos Panoramic200A system provides a 200 degrees field of view, which may be useful in selected cases where simultaneous view of the posterior pole and periphery is important. The Optos fluorescein angiogram directed the management of our patient with proliferative diabetic retinopathy combined with asteroid hyalosis.

Choroidal neovascular membrane secondary to primary hemochromatosis.

PURPOSE: To describe the findings for a patient with hemochromatosis, angioid streak-like changes, and choroidal neovascularization. METHODS: Case report. RESULTS: A 63-year-old man with primary hemochromatosis presented with recent vision loss. Visual acuity was 20/20 in the right eye and 20/70 in the left eye. Funduscopic examination and fluorescein angiography disclosed diffuse retinal pigment epithelial mottling, peripapillary hyperfluorescence, and a choroidal neovascular membrane lesion. CONCLUSION: Hemochromatosis may be associated with angioid streak-like changes in Bruch membrane, choroidal neovascularization, and diffuse retinal pigment epithelial changes.

Extended follow-up of small melanocytic choroidal tumors treated with transpupillary thermotherapy.

OBJECTIVE: To report our longer-term follow-up observations in patients with small choroidal melanomas primarily treated with transpupillary thermotherapy (TTT). METHODS: In this noncomparative interventional case series, 40 patients with small melanocytic tumors of the choroid (thickness <3.5 mm) underwent TTT. Follow-up examinations including ophthalmoscopy, ultrasonography, and fundus photography were conducted at 24 to 48 hours, 2 to 6 weeks, and 6-month intervals after treatment. RESULTS: Forty patients (mean age, 58 years) with small melanocytic tumors underwent TTT. Mean follow-up in all patients was 42 months. In most cases TTT resulted in tumor regression. Thirty-one (77.5%) of 40 tumors did not recur after initial treatment with TTT. In 5 (12.5%) of 40 tumors with initial basal diameters ranging from 4 x 2.75 mm to 7.5 x 6 mm and a mean initial thickness of 2.0 mm, edge recurrences developed, which were satisfactorily treated with additional TTT (4 cases) or cryotherapy (1 case). The mean interval between initial TTT and recurrence in this subgroup was 15 months (range, 7-22 months). Of 36 eyes that were successfully treated with TTT or cryotherapy, 26 eyes (72%) had posttreatment visual acuity better than or equal to pretreatment visual acuity. Four (10%) of 40 tumors were not controlled with TTT and eventually required brachytherapy (n = 1), proton radiation (n = 1), or enucleation (n = 2). The initial basal diameters of these tumors ranged from 7.5 x 7.5 mm to 9 x 7.5 mm, with a mean initial thickness of 2.6 mm. The mean interval between treatment and determination of treatment failure was 22 months (range, 7-30 months). CONCLUSIONS: Transpupillary thermotherapy resulted in tumor regression of most small melanocytic choroidal tumors. Tumor edge recurrences were successfully treated with additional TTT in most cases. Four tumors required irradiation or enucleation because of treatment failures with TTT. Transpupillary thermotherapy as a stand-alone therapy is insufficient for some small choroidal melanomas.