Development of Age-Related Macular Degeneration (AMD) in the Fellow Eye of Patients with AMD Treated by Treat-and-Extend Intravitreal Therapy with Aflibercept.

PURPOSE: To evaluate the development of neovascular age-related macular degeneration (nAMD) in the fellow eye in patients with unilateral nAMD treated by a treat-and-extend (TAE) regimen with intravitreal aflibercept injections. METHODS: We retrospectively studied 104 patients with treatment-naïve unilateral nAMD. We assessed best-corrected visual acuity (BCVA) and exudative changes in the treated eyes and development of nAMD in the fellow eye for 2 years. RESULTS: The subjects included 46 patients with typical AMD (tAMD), 44 with polypoidal choroidal vasculopathy (PCV), and 14 with retinal angiomatous proliferation (RAP). BCVA was significantly improved after the loading phase in all subtypes. Forty-six patients (44.2%) had no recurrence within 2 years after the loading phase, including 12 (26.1%) with tAMD, 23 (52.2%) with PCV, and 11 (78.6%) with RAP (p < 0.01). Eleven patients (10.6%) developed nAMD in the fellow eye within 2 years, including 4 (8.7%) with tAMD, 0 (0%) with PCV, and 7 (50.0%) with RAP (p < 0.001). CONCLUSIONS: Patients with RAP had significantly more frequent development of nAMD in the fellow eye compared to other subtypes, while they showed significantly less recurrence during the TAE regimen with intravitreal aflibercept injections. Development of nAMD in the fellow eye should be monitored in RAP when the injection interval is extended.

Genetic analysis of varicella-zoster virus in the aqueous humor in uveitis with severe hyphema.

BACKGROUND: Genetic variations have been identified in the genome of varicella-zoster virus (VZV) strains using vesicle fluid, varicella scabs and throat swab samples. We report a rare case of VZV-associated uveitis with severe hyphema, which was immediately diagnosed by polymerase chain reaction (PCR) using the aqueous humor, in which we were able to analyze the VZV genotype for the first time. CASE PRESENTATION: A 16-year-old Japanese boy was referred to our hospital with a 20-day history of unilateral anterior uveitis and 11-day history of hyphema. At presentation, details of the iris, the iridocorneal angle, and the fundus were not visible due to the severe hyphema. Serum anti-VZV IgG and anti-VZV IgM were elevated, and 1.61 × 109 copies/mL of VZV-DNA were detected by real-time PCR using the aqueous humor. As there were no eruptions on his face or body, we diagnosed zoster sine herpete and started intravenous administration of prednisolone and acyclovir. The hyphema completely disappeared 2 weeks after presentation, while sectorial iris atrophy and mild periphlebitis of the fundus became gradually apparent. Anterior inflammation and periphlebitis gradually improved and VZV-DNA in the aqueous humor was reduced to 1.02 × 106 copies/mL at 4 weeks after presentation. Examination by slit lamp microscope revealed no inflammation after 5 months, and VZV-DNA could no longer be detected in the aqueous humor. Serum anti-VZV IgG and anti-VZV IgM also showed a gradual decrease along with improvement in ocular inflammation. The genetic analysis of multiple open reading frames and the R5 variable repeat region in the VZV genes, using DNA extracted from the aqueous humor at presentation, showed that the isolate was a wild-type clade 2 VZV strain (prevalent in Japan and surrounding countries) with R5A allele and one SNP unique to clade 1 (both are major types in Europe and North America). CONCLUSIONS: VZV-associated uveitis may develop hyphema that obscures ocular inflammation, thus PCR analysis using the aqueous humor is the key investigation necessary for the diagnosis. The measurement of VZV-DNA copies by real-time PCR would be useful for evaluation of therapeutic effects. We could amplify and analyze VZV genotype using the aqueous humor including a very large number of VZV-DNA copies (1.61 × 109 copies/mL).

Two-year results of a treat-and-extend regimen with aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the effects of aflibercept therapy using a treat-and-extend regimen on treatment-naïve polypoidal choroidal vasculopathy (PCV). METHODS: In a retrospective interventional case series of 58 eyes of 58 patients with PCV, we assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and number of injections for 2 years. Polypoidal lesions were also evaluated before treatment and after the loading phase by indocyanine green angiography. RESULTS: BCVA significantly improved after the loading phase and was maintained in the maintenance phase. CMT and CCT significantly reduced after the loading phase and were maintained throughout the follow-up period. The number of injections averaged 7.72 in the first year and 4.67 in the second year. The average number of polypoidal lesions per patient was 2.43 before treatment. In 32 patients (55.2%), polypoidal lesions regressed completely after the loading phase; these patients also needed significantly fewer injections compared to other patients. CCT at baseline was positively correlated with the decreased amount of CCT after 2 years and negatively correlated with the number of injections for 2 years. CONCLUSIONS: Treat-and-extend intravitreal therapy with aflibercept may be effective for improving BCVA and exudative change in eyes with PCV. The regression of polypoidal lesions after the loading phase and thicker choroid at baseline might lead to fewer total number of intravitreal injections of aflibercept.

Two-Year Outcomes of a Treat-and-Extend Regimen Using Intravitreal Aflibercept Injections for Typical Age-Related Macular Degeneration.

PURPOSE: The aim of this study was to evaluate the efficacy of a treat-and-extend (TAE) regimen using intravitreal injection of aflibercept (IVA) for typical age-related macular degeneration (tAMD). METHODS: We retrospectively studied 61 treatment-naïve eyes with tAMD. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), number of injections, and complications during 2 years were evaluated. RESULTS: BCVA significantly improved by on average 0.13 logMAR units, and CMT and CCT significantly decreased after 2 years. The number of injections was on average 13.6. In the second year, eyes with classic choroidal neovascularization (CNV) needed significantly fewer treatments than eyes with occult CNV. Fourteen eyes, which developed subfoveal fibrosis, showed significantly poorer BCVA after 2 years. Subfoveal fibrosis was significantly common in classic CNV. CONCLUSION: A TAE regimen using IVA for tAMD might be effective for improving BCVA and exudative changes. The exudation may be suppressed with fewer treatments in classic CNV compared to occult CNV.

TREAT-AND-EXTEND REGIMEN WITH AFLIBERCEPT FOR RETINAL ANGIOMATOUS PROLIFERATION.

PURPOSE: To evaluate the effects of aflibercept therapy using a treat-and-extend regimen on treatment-naïve retinal angiomatous proliferation (RAP) and development of retinal pigment epithelium (RPE) atrophy. METHODS: We retrospectively studied 17 treated eyes with RAP and 13 untreated fellow eyes. We assessed best-corrected visual acuity (BCVA) in logarithm of the minimal angle of resolution (logMAR) units and recorded the total number of injections for 12 months. Central macular thickness (CMT) and central choroidal thickness (CCT) were assessed by optical coherence tomography (OCT), and RPE atrophy extent in the macular area was assessed by fundus autofluorescence. RESULTS: Average BCVA in eyes with RAP was 0.57 logMAR units (Snellen 20/74 or approximately 56.5 ETDRS letters) before treatment and significantly improved to 0.38 (Snellen 20/48 or approximately 66 ETDRS letters, P < 0.01) after 3 months and 0.32 (Snellen 20/42 or approximately 69 ETDRS letters, P < 0.01) after 12 months. Average CMT was 340 µm before treatment and significantly reduced to 133 µm (P < 0.001) after 3 months and 130 µm (P < 0.001) after 12 months. Average CCT was 147 µm before treatment, 123 µm (P < 0.01) after 3 months, and 131 µm (P < 0.01) after 12 months. Average total number of injections was 7.2. Average area of RPE atrophy enlarged by 1.00 mm in treated eyes compared with 0.34 mm in fellow eyes (P < 0.01). The enlarged area of RPE atrophy was inversely correlated with central choroidal thickness after 12 months (rs = -0.49, P < 0.01) and positively correlated with the number of injections (rs = 0.58, P < 0.01). CONCLUSION: Treat-and-extend intravitreal therapy with aflibercept may be effective for improvement and stabilization of visual acuity and exudative change in eyes with RAP. However, choroidal thinning during the treatment regimen may accelerate enlargement of RPE atrophy.

Treat-and-Extend Regimen with Aflibercept for Neovascular Age-Related Macular Degeneration: Efficacy and Macular Atrophy Development.

PURPOSE: To evaluate the effects of intravitreal injection of aflibercept using a treat-and-extend dosing regimen on treatment-naïve neovascular age-related macular degeneration (AMD) and the development of macular atrophy. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Eyes (n = 137) with treatment-naïve neovascular AMD, including 18 eyes with typical AMD with classic choroidal neovascularization (CNV), 44 eyes with typical AMD with occult CNV, 58 eyes with polypoidal choroidal vasculopathy, and 17 eyes with retinal angiomatous proliferation (RAP). METHODS: Clinical records of eyes with neovascular AMD that underwent 3 consecutive monthly intravitreal injections of aflibercept followed by a treat-and-extend dosing regimen were reviewed, and the corresponding imaging studies were analyzed. MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and the extent of macular atrophy in the macular area during a 2-year follow-up period. RESULTS: In all subtypes after 1 and 2 years, CMT and CCT were reduced significantly, whereas macular atrophy showed significant enlargement. At baseline, the extent of macular atrophy was greater in RAP than other subtypes; after 2 years, the macular atrophy enlargement was also greatest in RAP and correlated negatively with CCT (rs = -0.72; P < 0.01). Best-corrected visual acuity showed significant improvement after 1 and 2 years in all subtypes other than RAP. In RAP, BCVA was improved significantly after 1 year, but the magnitude of this improvement lost statistical significance after 2 years. CONCLUSIONS: Treat-and-extend with intravitreal aflibercept may be effective for improving BCVA and ameliorating exudative changes in neovascular AMD. However in RAP, choroidal thinning during the treatment regimen may accelerate enlargement of macular atrophy, thereby diminishing the improvement in BCVA after 2 years.

Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

PURPOSE: To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). METHODS: We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. RESULTS: The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). CONCLUSION: Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.