Felix Y. Chau

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab

PurposeThe aim of this study is to report the short-term efficacy of aflibercept in the treatment of neovascular age-related macular degeneration (AMD) with associated retinal pigment epithelial detachment (PED) which is refractory or develops tachyphylaxis to bevacizumab and ranibizumab.MethodsThe method comprised a retrospective review of the medical records of patients with neovascular AMD and associated PEDs recently treated with aflibercept and previously treated with bevacizumab and ranibizumab.ResultsThree eyes of three female patients of ages 49, 55, and 65 years old with large serous PEDs and subretinal fluid (SRF) associated with occult choroidal neovascularization and neovascular AMD were treated with aflibercept after intravitreal bevacizumab and/or ranibizumab failed to resolve the lesions. All had complete resolution of SRF and complete or near-complete resolution of the PEDs after aflibercept injections over a 3-month period. Visual acuity improved in all three eyes.ConclusionIntravitreal aflibercept may be an effective treatment option for serous PED in neovascular AMD patients after bevacizumab and ranibizumab have previously failed. Larger studies with longer follow-up are required to determine the role of aflibercept in treatment of PED in neovascular AMD.

Central Macular Splaying and Outer Retinal Thinning in Asymptomatic Sickle Cell Patients by Spectral Domain Optical Coherence Tomography

PURPOSE To investigate the prevalence and degree of macular thinning on optical coherence tomography (SDOCT) in African-American female patients with asymptomatic sickle cell disease. DESIGN Prospective comparative case series. METHODS Twenty-one sickle cell patients (42 eyes) without other systemic or ocular diseases and 18 healthy control patients (33 eyes) underwent SD-OCT. Images were manually segmented to measure inner retinal thickness (IRT) and outer retinal thickness (ORT). Central macular (central 1 mm), parafoveal (0.5-1.5 mm eccentricity), and perifoveal (1.5-3 mm eccentricity) thickness measurements were obtained in sickle cell patients and age/gender/race-matched healthy control subjects. RESULTS Central macular total thickness (CMT) in sickle cell patients was 220 ± 3 μm (mean ± SEM), which was significantly lower (P < .05) than controls (228 ± 3 μm). Parafoveal regions had thickness measurements of 314 ± 5 μm (nasal) and 304 ± 2 μm (temporal), which were significantly lower than controls (327 ± 2 μm and 311 ± 2 μm nasally and temporally, respectively) (P < .03, P < .043). There was also no significant difference in IRT in central macula, parafoveal, and perifoveal regions. Central macular ORT was 175 ± 2 μm vs 185 ± 1 μm in controls (P < .0002). ORT in temporal parafoveal and perifoveal regions was 142 ± 2 μm and 120 ± 1 μm, respectively, vs 150 ± 1 μm and 122 ± 1 μm in controls (P < .001 and P = .16, respectively). CONCLUSIONS Manual segmentation of SD-OCT images revealed significant total retinal thinning in the central macula and splaying in asymptomatic sickle cell patients. Retinal thinning was predominately in outer retinal layers in central macula and parafoveal regions.

Fluorescein Angiography of Recurrent Retinopathy of Prematurity After Initial Intravitreous Bevacizumab Treatment

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271-2284. 2. Nagpal A, Vora R, Margolis TP, Acharya NR. Interstitial keratitis following varicella vaccination. Arch Ophthalmol. 2009;127(2):222-223. 3. Naseri A, Good WV, Cunningham ET Jr. Herpes zoster virus sclerokeratitis and anterior uveitis in a child following varicella vaccination. Am J Ophthalmol. 2003;135(3):415-417. 4. Naseri A, Margolis TP. Varicella zoster virus immune recovery stromal keratitis in a patient with AIDS. Br J Ophthalmol. 2001;85(11):1390-1391.

Peripapillary retinal nerve fiber layer thickness in sickle-cell hemoglobinopathies using spectral-domain optical coherence tomography

PURPOSE To determine whether patients with a sickle-cell hemoglobinopathy without glaucoma have peripapillary retinal nerve fiber layer (RNFL) thinning by spectral-domain optical coherence tomography. DESIGN Prospective study. METHODS All patients with a sickle cell hemoglobinopathy (sickle-cell disease, sickle-cell hemoglobin C disease, and sickle-cell thalassemia) and age-similar, race-matched controls underwent a comprehensive eye examination and spectral-domain optical coherence tomography of the macula and optic nerve head using the Heidelberg Spectralis (Heidelberg Engineering, Inc, Carlsbad, California, USA). Participants with prior retinal treatments (laser or surgery), diabetes mellitus, glaucoma, or other ocular diseases were excluded. The sickle-cell disease patients were grouped into those with focal macular thinning and those without. Those with macular thinning were grouped further into mild, moderate, and severe thinning groups based on temporal macular thickness. Analysis of variance testing and post hoc analysis with the Tukey test and Pearson correlation were performed to assess for peripapillary RNFL thickness differences among different groups. RESULTS One hundred fifty-one eyes of 88 sickle-cell patients and 55 eyes of 30 age-similar and race-matched (black) controls were included. Sickle-cell patient eyes with macular thinning (n = 81) had thinner mean peripapillary RNFL thicknesses in the nasal sector (P = .01) compared with non-sickle-cell control eyes and in the superotemporal sector (P = .01) compared with sickle-cell patient eyes without macular thinning (n = 70). In the severe macular thinning subgroup (n = 55), the mean peripapillary RNFL thickness was significantly thinner than that of controls (P < .05) in 6 of 7 sectors. There is a positive linear relationship between temporal macular thickness and global peripapillary RNFL thickness with a Pearson correlation coefficient of 0.60 (P < .0001). CONCLUSIONS Nonglaucomatous, black sickle-cell patients with focal macular thinning on spectral-domain optical coherence tomography have significantly thinner peripapillary RNFL than those without macular thinning or controls. The degree of thinning correlates with severity of temporal macular thinning. These patients may require different peripapillary RNFL thickness thresholds for future glaucoma evaluations.

Laser Photocoagulation at Birth Prevents Blindness in Norrie's Disease Diagnosed Using Amniocentesis

OBJECTIVE To report the first case of prophylactic laser treatment to prevent blindness in a patient who was diagnosed with Norries disease by genetic testing with amniocentesis. DESIGN Case report. PARTICIPANTS A 2-year-old white boy with Norries disease. METHODS A 37-week gestational age male with a family history of Norries disease was born via Cesarean section after the mother had undergone prenatal amniocentesis fetal-genetic testing at 23 weeks of gestation. A C520T (nonsense) mutation was found in the Norries disease gene. After examination under anesthesia confirmed the diagnosis on the first day of life, laser photocoagulation was applied to the avascular retina bilaterally. The patient was followed closely by ophthalmology, pediatrics, and occupational therapy departments. MAIN OUTCOME MEASURES Functional outcome, as documented by Teller visual acuity and formal occupational therapy testing, and anatomic outcome, as documented by Retcam photography and fluorescein angiography. RESULTS Complete regression of extraretinal fibrovascular proliferation was observed 1 month after laser treatment. No retinal detachment had occurred to date at 24 months. Teller visual acuity at 23 months of life was 20/100 in both eyes. The patients vision and developmental milestones were age appropriate. CONCLUSIONS Pre-term genetic diagnosis with immediate laser treatment after birth may preserve vision in individuals affected with Norries disease.

Outcomes of pars plana glaucoma drainage implant in Boston type 1 keratoprosthesis surgery.

Purpose:Glaucoma drainage implantation in conjunction with Boston Type 1 Keratoprosthesis placement is a surgical option in controlling postoperative glaucoma. The purpose of this study is to report outcomes of combined pars plana vitrectomy and glaucoma drainage implantation with corneal patch graft in Boston Type 1 Keratoprosthesis patients. Patients and Methods:A retrospective review of patients who underwent pars plana glaucoma drainage implantation in combination with Boston Type 1 Keratoprosthesis was performed. Preoperative and postoperative parameters collected and analyzed included: visual acuity, intraocular pressure, number of glaucoma medications to achieve intraocular pressure control, bandage contact lens fit, and postoperative complications. Results:Twenty eyes of 20 patients were identified; 95% had preoperative diagnosis of glaucoma, utilizing on an average 2.5 medications with an average intraocular pressure of 19.8 mm Hg (±6.3 mm Hg; range, 9 to 32.8 mm Hg). After placement of the pars plana glaucoma drainage implant, an average intraocular pressure of 19 mm Hg (±7.0 mm Hg; range, 8 to 30 mm Hg) by scleral pneumotonometry was achieved and 85% were deemed to have normal pressures by digital palpation. An average of 2.1 intraocular pressure-lowering medications were required on last follow-up. Average follow-up was 31.6 months (±17.4 mo; range, 12.3 to 71.6 mo). Two eyes required glaucoma drainage implant explantation: one eye due to endophthalmitis from a nonhealing corneal ulcer and the other eye due to corneal melt. None of our patients experienced conjunctival erosion over a pars plana positioned glaucoma drainage implant or tube. Conclusions:For the long-term management of glaucoma in keratoprosthesis patients, a posteriorly placed pars plana glaucoma drainage implant with corneal patch graft in conjunction with keratoprosthesis has a low risk of erosion and postoperative complications.

In vivo retinal vascular oxygen tension imaging and fluorescein angiography in the mouse model of oxygen-induced retinopathy.

PURPOSE Oxygenation abnormalities are implicated in the development of retinopathy of prematurity (ROP). The purpose of this study is to report in vivo retinal vascular oxygen tension (PO2) measurements and fluorescein angiography (FA) findings in the mouse model of oxygen-induced retinopathy (OIR). METHODS We exposed 19 neonatal mice to 77% oxygen from postnatal day 7 (P7) to P12 (OIR), while 11 neonatal mice were kept under room air (control). Using phosphorescence lifetime imaging, retinal vascular PO2 was measured followed by FA. Repeated measures ANOVA was performed to determine the effects of blood vessel type (artery and vein) and group (OIR and control) on PO2. Avascular retinal areas were measured from FA images in OIR mice. RESULTS There was a significant effect of vessel type on PO2 (P < 0.001). The effect of group on PO2 was not significant (P = 0.3), indicating similar PO2 between OIR and control mice. The interaction between group and vessel type was significant (P = 0.03), indicating a larger arteriovenous PO2 difference in OIR mice than control mice. In control mice, FA displayed normal vascularization, while FA of OIR mice showed abnormalities, including dilation and tortuosity of major retinal blood vessels, and avascular regions. In OIR mice, the mean percent avascular retinal area was 33% ± 18%. CONCLUSIONS In vivo assessment of retinal vascular oxygen tension and vascularization patterns demonstrated abnormalities in the mouse model of OIR. This approach has the potential to improve understanding of retinal vascular development and oxygenation alterations due to ROP and other ischemic retinal diseases.

Wavefront error correction with adaptive optics in diabetic retinopathy.

Purpose To determine the effects of diabetic retinopathy (DR), increased foveal thickness (FT), and adaptive optics (AO) on wavefront aberrations and Shack-Hartmann (SH) image quality. Methods Shack-Hartmann aberrometry and wavefront error correction were performed with a bench-top AO retinal imaging system in 10 healthy control and 19 DR subjects. Spectral domain optical coherence tomography was performed and central FT was measured. Based on the FT data in the control group, subjects in the DR group were categorized into two subgroups: those with normal FT and those with increased FT. Shack-Hartmann image quality was assessed based on spot areas, and high-order (HO) root mean square (RMS) and total RMS were calculated. Results There was a significant effect of DR on HO and total RMS (p = 0.01), and RMS decreased significantly after AO correction (p < 0.001). Shack-Hartmann spot area was significantly affected by DR (p < 0.001), but it did not change after AO correction (p = 0.6). High-order RMS, total RMS, and SH spot area were higher in DR subjects both before and after AO correction. In DR subgroups, HO and total RMS decreased significantly after AO correction (p < 0.001), whereas the effect of increased FT on HO and total RMS was not significant (p ≥ 0.7). There were no significant effects of increased FT and AO on SH spot area (p = 0.9). Conclusions Diabetic retinopathy subjects had higher wavefront aberrations and less compact SH spots, likely attributable to pathological changes in the ocular optics. Wavefront aberrations were significantly reduced by AO, although AO performance was suboptimal in DR subjects as compared with control subjects.

Retinal Oximetry and Vessel Diameter Measurements With a Commercially Available Scanning Laser Ophthalmoscope in Diabetic Retinopathy

Purpose To test the hypothesis that retinal vascular diameter and hemoglobin oxygen saturation alterations, according to stages of diabetic retinopathy (DR), are discernible with a commercially available scanning laser ophthalmoscope (SLO). Methods One hundred eighty-one subjects with no diabetes (No DM), diabetes with no DR (No DR), nonproliferative DR (NPDR), or proliferative DR (PDR, all had photocoagulation) underwent imaging with an SLO with dual lasers (532 nm and 633 nm). Customized image analysis software determined the diameters of retinal arteries and veins (DA and DV) and central retinal artery and vein equivalents (CRAE and CRVE). Oxygen saturations of hemoglobin in arteries and veins (SO2A and SO2V) were estimated from optical densities of vessels on images at the two wavelengths. Statistical models were generated by adjusting for effects of sex, race, age, eye, and fundus pigmentation. Results DA, CRAE, and CRVE were reduced in PDR compared to No DM (P ≤ 0.03). DV and CRVE were similar between No DM and No DR, but they were higher in NPDR than No DR (P ≤ 0.01). Effect of stage of disease on SO2A differed by race, being increased relative to No DM in NPDR and PDR in Hispanic participants only (P ≤ 0.02). Relative to No DM, SO2V was increased in NPDR and PDR (P ≤ 0.05). Conclusions Alterations in retinal vascular diameters and SO2 by diabetic retinopathy stage can be detected with a widely available SLO, and covariates such as race can influence the results.

The effects of diabetic retinopathy stage and light flicker on inner retinal oxygen extraction fraction

Purpose We determined the effects of light flicker and diabetic retinopathy (DR) stage on retinal vascular diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF). Methods Subjects were categorized as nondiabetic control (NC, n = 42), diabetic with no clinical DR (NDR; n = 32), nonproliferative DR (NPDR; n = 42), or proliferative DR (PDR; n = 14). Our customized optical imaging system simultaneously measured arterial and venous D (DA, DV) and SO2 (SO2A, SO2V) before and during light flicker. Inner retinal OEF was derived from SO2 values. Light flicker–induced ratios of metrics (DAR, DVR, SO2AR, SO2VR, OEFR) were calculated. Results Arterial D was larger in NPDR compared to NC (P = 0.01) and PDR (P = 0.002), whereas DV was similar among groups (P ≥ 0.16). Light flicker increased DA and DV (P ≤ 0.004), but DAR and DVR were similar among groups (P ≥ 0.09). Arterial SO2 was higher in all groups compared to NC (P ≤ 0.02) and higher in PDR compared to NDR and NPDR (P<0.001). Arterial SO2 did not change with light flicker (P ≥ 0.1). Venous SO2 was higher in NPDR and PDR compared to NC and NDR (P ≤ 0.02). Light flicker increased SO2V in NC, NDR, and PDR (P ≤ 0.003), and SO2VR was lower in NPDR compared to NC and NDR (P ≤ 0.05). Inner retinal OEF was lower in NPDR compared to NDR and PDR (P ≤ 0.02). Light flicker decreased OEF (P ≤ 0.03), but OEFR was greater in NPDR compared to NC and NDR (P ≤ 0.03). Conclusions The findings of alterations in retinal D, SO2, OEF, and their light flicker–induced responses at stages of DR may be useful to elucidate the pathophysiology of DR.