Palmetto Retina Center

To report the efficacy, durability, and safety of intravitreal aflibercept 8 mg versus intravitreal aflibercept 2 mg every 8 weeks (2q8) in patients with neovascular age-related macular degeneration (nAMD) through 96 weeks, PULSAR (ClinicalTrials.gov identifier, NCT04423718). Phase 3, randomized, noninferiority, 96-week trial. Treatment-naive adults ≥ 50 years with nAMD. Patients were randomized 1:1:1 to intravitreal aflibercept 8 mg every 12 or 16 weeks (8q12 or 8q16), or 2q8, after 3 initial monthly doses; dosing intervals in 8-mg groups were modified based on prespecified criteria. Change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), proportion of patients maintaining or extending the randomized dosing intervals, and safety outcomes. Of 1009 patients treated, 869 patients (8q12, n = 291; 8q16, n = 292; 2q8, n = 286) completed treatment through week 96. Least squares (LS) mean change from baseline in BCVA at week 96 was +5.6 (95% confidence interval [Cl], 4.1-7.1), +5.5 (95% Cl, 4.0-7.0), and +6.6 (95% Cl, 5.2-8.0) letters in the 8q12, 8q16, and 2q8 groups, respectively; 8q12 and 8q16 differences versus 2q8 in LS mean BCVA changes at week 96 met the noninferiority criteria specified for the primary end point at week 48. Mean (standard deviation) change in CRT from baseline was -143.9 (123.6) μm, -153.4 (140.8) μm, and -135.8 (133.1) μm in the 8q12, 8q16, and 2q8 groups, respectively. Patients completing 96 weeks of treatment in the 8q12, 8q16, and 2q8 groups received a mean of 9.7, 8.2, and 12.8 active injections, respectively. Of these, 87% of patients in the 8q12 group had last assigned dosing intervals of 12 weeks or more, whereas 78%, 53%, and 31% of patients in the 8q16 group qualified for last assigned dosing intervals of ≥ 16 weeks, ≥ 20 weeks, and 24 weeks, respectively. Incidence of ocular treatment-emergent adverse events was similar across groups. Aflibercept 8 mg delivered sustained disease control in patients with nAMD, maintaining improvements in visual and anatomic outcomes through week 96 with extended dosing intervals and similar safety profile to aflibercept 2 mg. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background/aimsTo evaluate the efficacy and safety of individualised 2.0 mg intravitreal aflibercept retreatment for diabetic macular oedema (DME) through the fifth year of management.MethodsThis is a phase IV, 2-year, open-label extension study. Sixty patients completing the 3-year VISTA DME (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) phase III trial enrolled in the ENDURANCE (Long-Term Efficacy and Safety of Intravitreal Aflibercept for the Treatment of DME in Subjects Who Completed the VISTA DME Trial) extension study. All patients received aflibercept in the presence of clinically relevant DME. Intervals between visits were prescribed according to disease activity. The main outcome measure was mean aflibercept injections given through 2 years.ResultsA mean of 7.7 aflibercept injections were administered through 2 years. Fifteen (25%) patients required no retreatment and 48% (n=29) of patients received five or fewer injections through 2 years. Among patients who received at least one aflibercept retreatment during ENDURANCE, the mean number of injections through 2 years was 9.5. The mean visual acuity and central retinal thickness gains achieved during VISTA DME were maintained and stable during ENDURANCE. The most notable safety signal was progression of diabetic retinopathy. Six (10%) patients converted from non-proliferative to proliferative diabetic retinopathy (PDR), and a total of eight patients experienced PDR events occurring at a mean of 387 days following the previous aflibercept treatment.ConclusionThe need for aflibercept retreatment was substantially reduced in the fourth and fifth years of aflibercept dosing for DME following initiation of therapy in the VISTA DME trial. While vision gains achieved during the 3-year VISTA DME trial were maintained through ENDURANCE with a reduced treatment burden, clinically relevant worsening of diabetic retinopathy was observed with progression to PDR in 10% of the eyes.Trial registration numberNCT02299336

I recently examined a patient with atypical features of central serous chorioretinopathy (CSC) (1) extending to the peripapillary region that mimicked the fundus findings of an optic neuropathy. A 43-year-old man presented with distorted vision in his left eye noted upon awakening that morning. He described the area of distorted vision as being slightly temporal to the center of fixation. He denied recent illness, pain on eye movements, photophobia, constitutional symptoms, or injuries to the eye. Past medical history was unremarkable. Past ocular history was significant for moderate myopia and a well-healed left upper lid laceration from a distant injury. He took no prescription medications, including no corticosteroid formulations, and only occasionally consumed alcohol or used tobacco products. Family history was noncontributory. Uncorrected visual acuity was 20/20 in the right eye and 20/60 in the left eye. The patient had been emmetropic in the past. On this examination, visual acuity improved to 20/20 in the left eye with +1.25 sph, indicating a new hyperopic shift. Ishihara plates were correctly identified by both eyes. However, mild red desaturation was reported in the left eye. The patient reported mild micropsia with the left eye, and Amsler grid testing confirmed vertical metamorphopsia just temporal to fixation. Confrontation visual fields were full. Intraocular pressures were 16 mm Hg in both eyes. Pupils were of equal size and constricted briskly to direct light without a relative afferent pupil defect (RAPD). Extraocular movements and alignment were normal, as was biomicroscopic examination of the anterior ocular segment. Ophthalmoscopy of the right eye disclosed faint retinal pigment epithelium (RPE) mottling within the fovea as the only abnormality. In the left eye, there were foveal pigmentary alterations and subretinal fluid. The optic disc margins were blurred without pallor or hemorrhage. There was circumferential subretinal fluid around the optic disc (Fig. 1A). OCT of the left macula and peripapillary region revealed fluid under the neurosensory retina (Fig. 1B). There was no retinal thickening.FIG. 1: Fundus photograph (A) of the left eye demonstrates optic nerve edema with a cuff of subretinal fluid surrounding the optic nerve. The macula demonstrates pigmentary alterations and evidence of subneurosensory fluid accumulation. A 6-mm horizontal optical coherence tomography (OCT) scan (B) demonstrates subretinal fluid adjacent to the optic nerve as well as in the macular region (asterisk).Humphrey visual field 24-2 was normal in the right eye and revealed mild paracentral depression temporally in the left eye. Fluorescein angiography in the left eye revealed four pinpoint foci of hyperfluorescence at the level of the RPE exhibiting increasing leakage through the later phases of the angiogram. The optic nerve margins were blurred, but there was no hyperfluorescence or leakage from the optic disc. There was no pooling of dye within the subretinal space around the optic nerve (Fig. 2).FIG. 2: Late-phase fluorescein angiography demonstrates areas of pinpoint hyperfluorescence without marked optic disc hyperfluorescence.Examination 2 months later was unchanged in the right eye. In the left eye, visual acuity had improved to 20/50, and the hyperopia and most of the subretinal fluid had disappeared. A creamy yellow-white subretinal lesion was now present immediately above the fovea. My patient exhibited CSC with subretinal fluid around the optic disc, a rarely reported set of findings in CSC. There was no evidence of optic nerve dysfunction as color vision and pupillary reactions were normal. No optic pit or optic nerve head drusen (ONHD) were seen by ophthalmoscopy, OCT, or fluorescein angiography with autofluorescence. Multiple simultaneous pinpoint leaks on fluorescein angiography are unusual in acute CSC but are not unusual in the chronic severe form of CSC called diffuse retinal pigment epitheliopathy. Although multiple pinpoint leaks can also occur in Harada disease, leukemic infiltration, hypertensive retinopathy, and various inflammatory conditions, but there was no clinical support for these entities in our patient. Brodsky (2) described a single case labeled as central serous papillopathy. He proposed that the neurosensory detachment emanated from a discrete area of capillary leakage within a nonexcavated optic disc. Ours is an atypical case of CSC with submacular retinal edema and peripapillary edema that mimicked optic disc edema. Admitting that extension of subretinal fluid to the peripapillary area is unusual in CSC, the complaints of metamorphopsia and micropsia, in the absence of a relative afferent pupil defect, identified a retinal origin of this condition. The complaint of red desaturation, so often encountered in optic neuropathy, may also be reported in CSC, as in this patient. David Johnson, MD Palmetto Retina Center West Columbia, South Carolina [email protected]

The Program of All-inclusive Care for the Elderly (PACE) is a long-term care delivery and financing innovation. A major goal of PACE is prevention of unnecessary use of hospital and nursing home care. PACE serves enrollees in day centers and clinics, their homes, hospitals and nursing homes. Beginning at On Lok in San Francisco, the PACE model has been successfully replicated across the country. In 1995, PACE was fully operational in 11 cities in nine states. To enroll in PACE, a person must be 55 years of age or older, be certified by the state as eligible for care in a nursing home and live in the program's defined geographical catchment area. PACE participants are ethnically diverse. In 1995, the average PACE enrollee was 80.0 years old and had an average of 7.8 medical conditions and 2.7 dependencies in Activities of Daily Living. A significant number have bladder incontinence (55%). Many enrollees (39%) live alone in the community, and 14% have no means of informal support. Medicare and Medicaid waivers allow delivery of services beyond the usual Medicare and Medicaid benefits. The PACE service delivery system is comprehensive, uses an interdisciplinary team for care management, and integrates primary and specialty medical care. PACE receives monthly capitation payments from Medicare and Medicaid. Patients ineligible for Medicaid pay privately. Outcomes of PACE programs have been positive. There has been steady census growth, good consumer satisfaction, reduction in use of institutional care, controlled utilization of medical services, and cost savings to public and private payers of care, including Medicare and Medicaid. However, starting up a PACE program requires substantial time and capital, and the model has not yet attracted large numbers of older middle income adults. The growing number of older people in the United States challenges healthcare providers and policy makers alike to provide high quality care in an environment of shrinking resources. The PACE model's comprehensiveness of health and social services, its cost-effective coordinated system of care delivery, and its method of integrated financing have wide applicability and appeal.