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Purpose To evaluate tumor vasculature with optical coherence tomography angiography (OCTA) in malignant iris melanomas and benign iris lesions. Design Cross-sectional observational clinical study. Participants Patients with iris lesions and healthy volunteers. Methods Eyes were imaged using OCTA systems operating at 1050- and 840-nm wavelengths. Three-dimensional OCTA scans were acquired. Iris melanoma patients treated with radiation therapy were imaged again after I-125 plaque brachytherapy at 6 and 18 months. Main Outcome Measures OCT and OCTA images, qualitative evaluation of iris and tumor vasculature, and quantitative vessel density. Results One eye each of 8 normal volunteers and 9 patients with iris melanomas or benign iris lesions, including freckles, nevi, and an iris pigment epithelial (IPE) cyst, were imaged. The normal iris has radially oriented vessels within the stroma on OCTA. Penetration of flow signal in normal iris depended on iris color, with best penetration seen in light to moderately pigmented irides. Iris melanomas demonstrated tortuous and disorganized intratumoral vasculature. In 2 eyes with nevi there was no increased vascularity; in another, fine vascular loops were noted near an area of ectropion uveae. Iris freckles and the IPE cyst did not have intrinsic vascularity. The vessel density was significantly higher within iris melanomas (34.5%±9.8%, P < 0.05) than in benign iris nevi (8.0%±1.4%) or normal irides (8.0%±1.2%). Tumor regression after radiation therapy for melanomas was associated with decreased vessel density. OCTA at 1050 nm provided better visualization of tumor vasculature and penetration through thicker tumors than at 840 nm. But in very thick tumors and highly pigmented lesions even 1050-nm OCTA could not visualize their full thickness. Interpretable OCTA images were obtained in 82% of participants in whom imaging was attempted. Conclusions This is the first demonstration of OCTA in iris tumors. OCTA may provide a dye-free, no-injection, cost-effective method for monitoring a variety of tumors, including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field., National Institutes of Health (U.S.) (Grants R01 EY023285, R01 EY024544, R01 EY018184, DP3 DK104397, UL1TR000128, and P30 EY010572

PURPOSE: To measure low perfusion areas (LPA) and focal perfusion loss (FPL) in the peripapillary retina using optical coherence tomographic angiography (OCTA) in glaucoma. DESIGN: Prospective observation study. PARTICIPANTS: Forty-seven primary open angle glaucoma (POAG) patients and 36 normal subjects were analyzed. METHODS: One eye of each subject was scanned using AngioVue 4.5-mm OCTA scan centered on the disc. En face nerve fiber layer plexus angiogram was generated. With the use of custom software, a capillary density map was obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 21×21 pixels. The low-perfusion map is defined by local capillary density below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The LPA parameter is the cumulative area and FPL is the percent capillary density loss (relative to normal mean) integrated over the LPA. The retinal nerve fiber layer (NFL) thickness was measured from ONH scan on AngioVue. MAIN OUTCOME MEASURES: Peripapillary retinal LPA, FPL and NFL thickness. RESULTS: Among POAG patients, 3 had pre-perimetric glaucoma and 44 had perimetric glaucoma, with visual field (VF) mean deviation (MD) of −5.14 ± 4.25 dB. LPA was 3.40 ± 2.29 mm(2) in POAG and 0.11 ± 0.18 mm(2) among normal subjects (P < 0.001). FPL was 21.8 ± 17.0 % in POAG and 0.3 ± 0.7% in normal subjects (P < 0.001). The diagnostic accuracy as measured by the area under the receiver operating curve was 0.965 for both LPA and FPL, with sensitivity of 93.7% at 95% specificity. The repeatability as measured by intraclass correlation coefficient was 0.977 for LPA and 0.958 for FPL. FPL had an excellent correlation with VF MD (Spearman’s rho= −0.843) which was significantly (P = 0.008) better than the correlation between NFL thickness and VF MD (rho = 0.760). The hemispheric difference correlation between FPL and VF (Spearman’s rho=0.770) was significantly (P < 0.001) higher than the hemispheric difference correlation between LPA and VF (rho = 0.595). CONCLUSIONS: The low-perfusion map and the LPA and FPL parameters are able to assess the location and severity of focal glaucoma damage with good agreement with VF.

Purpose To compare the newer formulae, the optical coherence tomography (OCT)-based intraocular lens (IOL) power formula (OCT formula) and the Barrett True-K formula (True-K), with the methods on the American Society of Cataract and Refractive Surgery (ASCRS) calculator in eyes with previous myopic LASIK/photorefractive keratectomy (PRK). Design Prospective case series. Participants A total of 104 eyes of 80 patients who had previous myopic LASIK/PRK and subsequent cataract surgery and IOL implantation. Methods By using the actual refraction after cataract surgery as target refraction, predicted IOL power for each method was calculated. The IOL prediction error (PE) was obtained by subtracting the predicted IOL power from the power of the IOL implanted. Main Outcome Measures Arithmetic IOL PEs, variances of mean arithmetic IOL PE, median refractive PE, and percent of eyes within 0.5 diopters (D) and 1.0 D of refractive PE. Results Optical coherence tomography produced smaller variance of IOL PE than did Wang-Koch-Maloney (WKM) and Shammas ( P P Conclusions The OCT and True-K No History are promising formulas. The ASCRS IOL calculator has been updated to include the OCT and Barrett True K formulas. Trial registration: Intraocular Lens Power Calculation After Laser Refractive Surgery Based on Optical Coherence Tomography (OCT IOL); Identifier: NCT00532051; www.ClinicalTrials.gov.

To detect macular perfusion defects in glaucoma using projection-resolved optical coherence tomography (OCT) angiography.Prospective observation study.A total of 30 perimetric glaucoma and 30 age-matched normal participants were included.One eye of each participant was imaged using 6×6-mm macular OCT angiography (OCTA) scan pattern by 70-kHz 840-nm spectral-domain OCT. Flow signal was calculated by the split-spectrum amplitude-decorrelation angiography algorithm. A projection-resolved OCTA (PR-OCTA) algorithm was used to remove flow projection artifacts. Four en face OCTA slabs were analyzed: the superficial vascular complex (SVC), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and all-plexus retina (SVC + ICP + DCP). The vessel density (VD), defined as the percentage area occupied by flow pixels, was calculated from en face OCTA. A novel algorithm was used to adjust the vessel density to compensate for local variations in OCT signal strength.Macular retinal VD, ganglion cell complex (GCC) thickness, and visual field (VF) sensitivity.Focal capillary dropout could be visualized in the SVC, but not the ICP and DVP, in glaucomatous eyes. In the glaucoma group, the SVC and all-plexus retinal VD (mean ± standard deviation: 47.2%±7.1% and 73.5%±6.6%) were lower than in the normal group (60.5%±4.0% and 83.2%±4.2%, both P0.001, t test). The ICP and DCP VD were not significantly lower in the glaucoma group. Among the overall macular VD parameters, the SVC VD had the best diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AROC). The accuracy was even better when the worse hemisphere (inferior or superior) was used, achieving an AROC of 0.983 and a sensitivity of 96.7% at a specificity of 95%. Among the glaucoma participants, the hemispheric SVC VD values were highly correlated with the corresponding GCC thickness and VF sensitivity (P0.003). The reflectance compensation step in VD calculation significantly improved repeatability, normal population variation, and correlation with VF and GCC thickness.On the basis of PR-OCTA, glaucoma preferentially affects perfusion in the SVC in the macula more than the deeper plexuses. Reflectance-compensated SVC VD measurement by PR-OCTA detected glaucoma with high accuracy and could be useful in the clinical evaluation of glaucoma.

To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders.Retrospective case series.Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD).Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography.The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings.Participants were followed up for a median of 5.6 years (range 0.3-20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients.Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

To map the corneal epithelial thickness with Fourier-domain optical coherence tomography (OCT) and to develop epithelial thickness-based variables for keratoconus detection.Cross-sectional observational study.One hundred forty-five eyes from 76 normal subjects and 35 keratoconic eyes from 22 patients.A 26,000-Hz Fourier-domain OCT system with 5-μm axial resolution was used. The cornea was imaged with a Pachymetry + Cpwr scan pattern (6-mm scan diameter, 8 radials, 1024 axial-scans each, repeated 5 times) centered on the pupil. Three scans were obtained at a single visit in a prospective study. A computer algorithm was developed to map the corneal epithelial thickness automatically. Zonal epithelial thicknesses and 5 diagnostic variables, including minimum, superior-inferior (S-I), minimum-maximum (MIN-MAX), map standard deviation (MSD), and pattern standard deviation (PSD), were calculated. Repeatability of the measurements was assessed by the pooled standard deviation. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.Descriptive statistics, repeatability, and AUC of the zonal epithelial thickness and diagnostic variables.The central, superior, and inferior epithelial thickness averages were 52.3 ± 3.6 μm, 49.6 ± 3.5 μm, and 51.2 ± 3.4 μm in normal eyes and 51.9 ± 5.3 μm, 51.2 ± 4.2 μm, and 49.1 ± 4.3 μm in keratoconic eyes. Compared with normal eyes, keratoconic eyes had significantly lower inferior (P = 0.03) and minimum (P0.0001) corneal epithelial thickness, greater S-I (P = 0.013), more negative MIN-MAX (P0.0001), greater MSD (P0.0001), and larger PSD (P0.0001). The repeatability of the zonal average, minimum, S-I, and MIN-MAX epithelial thickness variables were between 0.7 and 1.9 μm. The repeatability of MSD was better than 0.4 μm. The repeatability of PSD was 0.02 or better. Among all epithelial thickness-based variables investigated, PSD provided the best diagnostic power (AUC = 1.00). Using an PSD cutoff value of 0.057 alone gave 100% specificity and 100% sensitivity.High-resolution Fourier-domain OCT mapped corneal epithelial thickness with good repeatability in both normal and keratoconic eyes. Keratoconus was characterized by apical epithelial thinning. The resulting deviation from the normal epithelial pattern could be detected with very high accuracy using the PSD variable.Proprietary or commercial disclosure may be found after the references.

Objective To describe wavefront-guided (WFG) LASIK for the primary treatment of low to moderate levels of myopia and astigmatism and to examine the evidence on the safety and effectiveness of the procedure in comparison with conventional LASIK. Methods Literature searches conducted in 2004, 2005, 2006, and 2007 retrieved 209 unique references from the PubMed and Cochrane Library databases. The panel selected 65 articles to review, and of these, chose 45 articles that they considered to be of sufficient clinical relevance to submit to the panel methodologist for review. During the review and preparation of this assessment, an additional 2 articles were included. A level I rating was assigned to properly conducted, well-designed, randomized clinical trials; a level II rating was assigned to well-designed cohort and case-controlled studies; and a level III rating was assigned to case series, case reports, and poorly designed prospective and retrospective studies. In addition, studies that were conducted by laser manufacturers before device approval (premarket approval) were reviewed as a separate category of evidence. Results The assessment describes studies reporting results of WFG LASIK clinical trials, comparative trials, or both of WFG and conventional LASIK that were rated level II and level III. There were no studies rated as level I evidence. Four premarket approval studies conducted by 4 laser manufacturers were included in the assessment. The assessment did not compare study results or laser platforms because there were many variables, including the amount of follow-up, the use of different microkeratomes, and the level of preoperative myopia and astigmatism. Conclusions There is substantial level II and level III evidence that WFG LASIK is safe and effective for the correction of primary myopia or primary myopia and astigmatism and that there is a high level of patient satisfaction. Microkeratome and flap-related complications are not common but can occur with WFG LASIK, just as with conventional LASIK. The WFG procedure seems to have similar or better refractive accuracy and uncorrected visual acuity outcomes compared with conventional LASIK. Likewise, there is evidence of improved contrast sensitivity and fewer visual symptoms, such as glare and halos at night, compared with conventional LASIK. Even though the procedure is designed to measure and treat both lower- and higher-order aberrations (HOAs), the latter are generally increased after WFG LASIK. The reasons for the increase in HOA are likely multifactorial, but the increase typically is less than that induced by conventional LASIK. No long-term assessment of WFG LASIK was possible because of the relatively short follow-up (12 months or fewer) of most of the studies reviewed.

To use optical coherence tomography (OCT) to identify the specific retinal layers and macular regions damaged in glaucoma.Observational cross-sectional study.One hundred forty-nine participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: normal (N) perimetric glaucoma (PG), and glaucoma suspect and preperimetric glaucoma (GSPPG) with 44, 73, and 29 persons, respectively.The Zeiss Stratus OCT system (Carl Zeiss Meditec, Inc., Dublin, CA) was used to map the macula over a 6-mm diameter and to scan the circumpapillary nerve fiber layer (cpNFL). The macular OCT images were exported for automatic segmentation using software developed by the authors. The thickness of the macular nerve fiber layer (mNFL), ganglion cell layer (mGCL), inner plexiform layer (mIPL), inner nuclear layer (mINL), outer retinal layer (mORL), and total retinal thickness were measured. Thickness measurements of GSPPG and PG eyes were compared with those of N eyes. The ability to differentiate between GSPPG and PG eyes against N eyes was assessed by fractional loss, standardized deviation, and the area under the receiver operating characteristic curve.Area-weighted average thicknesses of retinal sublayers in the macula.The mNFL, mGCL, mIPL, and mINL were significantly (P0.001) thinner in both the GSPPG and PG eyes than in the N eyes. In PG eyes, mNFL, mGCL, and mIPL thinning was most severe (approximately 20%), mINL thinning was intermediate (7%), and mORL thinning was minimal (3%). The repeatability (coefficient of variation and intraclass correlation) of thickness measurements was improved by combining the mNFL, mGCL, and mIPL measurements as the inner retinal layer (mIRL). The mIRL was the best macular parameter for glaucoma diagnosis and had discriminant power comparable with that of the cpNFL. The fractional loss of mIRL thickness was most severe in the inferior perifoveal region for both the PG and GSPPG groups.Glaucoma leads to thinning of the mNFL, mGCL, mIPL, and mINL, even before detectable visual field changes occur. A combination of the 3 innermost layers seems to provide optimal glaucoma detection. Increasing the sampling of peripheral macula with a new OCT scan pattern may improve glaucoma diagnosis further.

Objective To describe LASIK for hyperopia, hyperopia with astigmatism, and mixed astigmatism and to examine the evidence to answer questions about the safety and efficacy of the procedure. Methods A literature search conducted for the years 1968 to 2002 retrieved 118 citations. During review and preparation of this article, an additional 2 articles were included. The panel members selected 36 articles for the panel methodologist to review and rate according to the strength of evidence. A level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a level II rating to well-designed cohort and case–control studies; and a level III rating to case series, case reports, and poorly designed prospective and retrospective studies. Results This assessment describes 5 nonrandomized interventional trials (level II), 3 nonrandomized comparative trials (level III), and 20 noncomparative case series (level III). Additionally, 6 single-case reports (level III) were included because they reported relevant complications, and 2 theoretical analyses (level III) were also considered. This assessment does not compare studies because many variables such as range of hyperopia, follow-up periods, lasers, microkeratomes, techniques, and surgeon experience have not been controlled. Conclusions For low ( 4 to 5 D). Utilizing hyperopic LASIK for the treatment of consecutive hyperopia and astigmatism is also effective, although the ability to reduce hyperopic astigmatism after radial keratotomy is limited. Although a variety of ablation profiles can be used to treat mixed astigmatism, very good visual results have been reported (levels II and III evidence). Serious adverse complications leading to permanent visual loss are possible but, fortunately, very rare. There are insufficient data to compare one laser system with another or one ablation profile with another.

Objective This document describes laser in situ keratomileusis (LASIK) for myopia and astigmatism and examines the evidence to answer key questions about the efficacy and safety of the procedure. Methods A literature search conducted for the years 1968 to 2000 retrieved 486 citations and an update search conducted in June 2001 yielded an additional 243 articles. The panel members reviewed 160 of these articles and selected 47 for the panel methodologist to review and rate according to the strength of evidence. A Level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a Level II rating is assigned to well-designed cohort and case-control studies; and a Level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. Results The assessment describes randomized controlled trials published in 1997 or later (Level I evidence) and more recent comparative and noncomparative case series (Level II and Level III evidence), focusing on results for safety and effectiveness. It is difficult to extrapolate results from these studies that are comparable to current practices with the most recent generation lasers because of the rapid evolution of LASIK technology and techniques. It is also difficult to compare studies because of variations in the range of preoperative myopia, follow-up periods, lasers, nomograms, microkeratomes and techniques, the time frame of the study, and the investigators' experience. Conclusions For low to moderate myopia, results from studies in the literature have shown that LASIK is effective and predictable in terms of obtaining very good to excellent uncorrected visual acuity and that it is safe in terms of minimal loss of visual acuity. For moderate to high myopia (>6.0 D), the results are more variable, given the wide range of preoperative myopia. The results are similar for treated eyes with mild to moderate degrees of astigmatism (

Objective This document describes intrastromal corneal ring segments (Intacs) inserts technology and examines the evidence to answer the key question about whether the treatment is safe and effective in correcting low myopia. Methods A literature search that was conducted in September 2000 retrieved 13 relevant citations, and the reference lists of these articles were consulted for additional citations. Panel members reviewed this information and articles were rated according to the strength of evidence. Results Prospective multicenter phase II and III clinical trials (Level II evidence rating) of Intacs inserts for myopia of −1.00 to −3.00 diopters (D), with a maximum of +1.00 D of astigmatism, enrolled a total of 452 subjects, with a total of 454 surgical attempts. The results from phase II and phase III were pooled for much of the analysis. At 1 year, 97% of patients who completed follow-up had 20/40 or better uncorrected visual acuity (UCVA). Seventy-four percent of patients had 20/20 or better UCVA. Ninety-two percent of eyes were within ±1 D of intended refractive correction, and 69% were within 0.5 D of intended refractive correction. At 3 months, 90% of patients had less than 1.0 D of change from the previous examination performed at 1 month. The ocular complication rate, which was defined as clinically significant events but not resulting in permanent sequelae, was 11% at 12 months. The adverse event rate was 1.1%, defined as a serious event if untreated. Nearly 9% of patients requested to have their inserts removed and a total of 3.8% of patients required a secondary surgical intervention. Conclusions To date, evidence suggests that low myopia (−1 to −3 D) in a well-defined group of patients who have a stable manifest refraction and less than +1.0 D of astigmatism can be treated with Intacs inserts with a reasonable assurance of safety and effectiveness. Additional clinical research is needed to determine the long-term effectiveness of treatment and the comparative safety, effectiveness, and costs with other treatment modalities, including laser-assisted in-situ keratomileusis (LASIK) and photorefractive keratectomy (PRK).

Purpose To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants A total of 5 normal subjects and 5 subjects with neovascular AMD were included. Methods A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3×3-mm area and comprised 200×200×8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measures The CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD., National Institutes of Health (U.S.) (Grant 1R01 EY023285-01), National Institutes of Health (U.S.) (Grant R01 EY013516), Rosenbaum's P30EY010572, National Institutes of Health (U.S.) (Clinical and Translational Science Award Grant UL1TR000128), Research to Prevent Blindness, Inc. (United States) (Grant R01-EY11289-26), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), German Research Foundation (DFG-HO-1791/11-1), German Research Foundation (DFG-GSC80-SAOT)

Ophthalmology Volume 123, Number 3, March 2016 Descemet stripping endothelial keratoplasty. Arch Ophthalmol 3. Kopplin LJ, Przepyszny K, Schmotzer B, et al. Relationship of Fuchs endothelial corneal dystrophy severity to central corneal thickness. Arch Ophthalmol 2012;130:433–9. 4. Wacker K, McLaren JW, Amin SR, et al. Corneal high-order aberrations and backscatter in Fuchs’ endothelial corneal dys- trophy. Ophthalmology 2015;122:1645–52. 5. McLaren JW, Bachman LA, Kane KM, Patel SV. Objective assessment of the corneal endothelium in Fuchs’ endothelial dystrophy. Invest Ophthalmol Vis Sci 2014;55:1184–90. Re: Spaide et al.: Volume-rendering optical coherence tomography angio- graphy of macular telangiectasia type 2 (Ophthalmology 2015;122:2261-9) We agree very much with Spaide et al 1 that a great advantage of optical coherence tomography (OCT) angiography is its 3-dimensional (3D) nature, and that color coding for the depth of vessels is a natural way to represent this 3D information. However, we think it is disingenuous for Dr Spaide to imply that he was the first to adapt this approach from CT and MR literature and apply it to OCT angiography. He wrote: TO THE EDITOR: Instead of imaging the average or densest voxel, volume rendering uses all the voxel values to make an image that retains the sense of depth and is less prone to image artifact. These methods were adapted to OCTA, which does not use dye, by Dr. Spaide. In fact, volume rendering of angiography and color coding of vessel depth had already been used by several groups since the early days of OCT angiography. Barton et al 2 reported volume rendering of skin vasculature detected by Doppler OCT as early as 1999. Zhao et al 3 had described 3D volume-rendered Doppler OCT angi- ography of port wine stain vasculature by 2001. Yasuno et al had described 3D volume-rendered OCT angiography of in vivo human macular and optic nerve head vessels in 2006. 4 Wang et al (Optics Express 2007) had shown 3D volume rendering of mouse cortical vessels. Fingler et al (Optics Express 2009) had demonstrated volume rendering of human retinal microvasculature. Vakoc et al (Nature Medicine 2009) had used color coding to render complex 3D vasculature in tumor and brain layers using OCT angiography. Mariampillai et al (Optics Letters), Srinivasan et al (Optics Letters), and Yu et al (Journal of Biomedical Optics) had all used volume rendering to visualize 3D vascular structures in 2010. Jia et al (Proceedings of the National Academy of Sciences 2015) had used color to separate shallower retinal circulation from deeper choroidal circulation using the en face slab visualization approach, as did Kim et al (Proceedings of the National Academy of Sciences 2013) for visualizing vascular beds in geographic atrophy. And pixel transparency of the retinal slab was adjusted to optimize the visualization of choroidal neovascularization. 5 We list these prior works here so the reader can appreciate the work of pioneers in this field. Z HONGPING C HEN , P H D 1 D AVID H UANG , MD, P H D 2 J OSEPH A. I ZATT , P H D 3 R UIKANG K. W ANG , P H D 4 e24 J OHN S. W ERNER , P H D 5 Y OSHIAKI Y ASUNO , P H D 6 Department of Biomedical Engineering, University of California at Irvine, Irvine, California; 2 Casey Eye Institute, Oregon Health & Science University, Portland, Oregon; 3 Department of Biomedical Engineering, Duke University, Durham, North Carolina; 4 Department of Biomedical Engineering, University of Washington, Seattle, Washington; 5 Department of Ophthalmology, University of California at Davis, Sacramento, California; 6 Institute of Applied Physics, University of Tsukuba, Tsukuba, Japan Financial Disclosure(s): The authors made the following disclosures: Z.C.: Grants e NIH, during the conduct of the study; Personal fees and Other: OCT Medical Imaging Inc., outside the submitted work; Patent pending, a patent issued, a patent licensed, and a patent with royalties paid. D.H.: has a significant financial interest in Carl Zeiss Meditec; Oregon Health & Science University (OHSU) and Dr. Huang has a significant financial interest in Optovue, Inc., a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU. J.A.I.: US Patent No. 6,735,463, “Doppler Flow Imaging Using Optical Coherence Tomography” with royalties paid to Leica Microsystems, Inc. R.K.W.: Grants e National Institutes of Health; Grants and Nonfinancial support e Carl Zeiss Meditec Inc., outside the submitted work. In addition, Dr. Wang has a patent Oregon Health & Science University with royalties paid to Carl Zeiss Meditec, Inc., and a patent University of Washington pending. Y.Y.: Grants e Japan Society for the Promotion of Science, Japan Science and Technology Agency, Topcon Corp., Nidek Inc., Canon, during the conduct of the study; Grants e Tomey Corp., outside the submitted work. Correspondence: David Huang, MD, PhD, Oregon Health & Science University, 3375 SW Terwilliger Boulevard, Portland, OR 97239. E-mail: davidhuang@ alum.mit.edu. References 1. Spaide RF, Klancnik JM Jr, Cooney MJ, et al. Volume- rendering optical coherence tomography angiography of macular telangiectasia type 2. Ophthalmology 2015;122:2261–9. 2. Kehlet Barton J, Izatt JA, Kulkarni MD, et al. Three-dimensional reconstruction of blood vessels from in vivo color Doppler op- tical coherence tomography images. Dermatology 1999;198: 3. Zhao Y, Brecke KM, Ren H, et al. Three-dimensional recon- struction of in vivo blood vessels in human skin using phase- resolved optical Doppler tomography. IEEE J Sel Top Quantum Electron 2001;7:931–5. 4. Makita S, Hong Y, Yamanari M, et al. Optical coherence angiography. Opt Express 2006;14:7821–40. 5. Jia Y, Bailey ST, Hwang TS, et al. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci U S A 2015;112:E2395–402. We wish to thank the authors for their letter and also thank them for reading our paper. 1 Volume rendering has been used in representation of both computed tomography and magnetic resonance imaging for more than 3 decades. Thus, the techniques used in our paper are not new. We suggest reading the quoted sentence in the context of the paragraph in which it was embedded. We stated that the previous REPLY

Objective To review the published literature for evaluation of the safety and outcomes of phakic intraocular lens (pIOL) implantation for the correction of myopia and myopic astigmatism. Methods Literature searches of the PubMed and Cochrane Library databases were conducted on October 7, 2007, and July 14, 2008. The PubMed search was limited to the English language; the Cochrane Library was searched without language limitations. The searches retrieved 261 references. Of these, panel members chose 85 papers that they considered to be of high or medium clinical relevance to this assessment. The panel methodologist rated the articles according to the strength of evidence. Results Two pIOLs have been approved by the US Food and Drug Administration (FDA): one iris-fixated pIOL and one posterior-chamber IOL. In FDA trials of iris-fixated pIOLs, uncorrected visual acuity (UCVA) was ≥20/40 in 84% and ≥20/20 in 31% after 3 years. In FDA trials of posterior-chamber pIOLs, UCVA was ≥20/40 in 81% and ≥20/20 in 41%. Satisfaction with the quality of vision with both types of pIOLs was generally high. Toric anterior- and posterior-chamber pIOLs have shown improved clinical results in European trials compared with spherical pIOLs. Comparative studies showed pIOLs to provide better best spectacle-corrected visual acuity (BSCVA) and refractive predictability and stability compared with LASIK and photorefractive keratectomy and to have a lower risk of retinal detachment compared with refractive lens exchange. Reported complications and long-term safety concerns include endothelial cell loss, cataract formation, secondary glaucoma (pupillary block, pigment dispersion), iris atrophy (pupil ovalization), and traumatic dislocation. Conclusions Phakic IOL implantation is effective in the correction of myopia and myopic astigmatism. In cases of high myopia of −8 diopters or more, pIOLs may provide a better visual outcome than keratorefractive surgeries and better safety than refractive lens exchange. The short-term rates of complications and loss of BSCVA are acceptable. Comprehensive preoperative evaluation and long-term postoperative follow-up examinations are needed to monitor for and prevent serious complications, and to establish long-term safety. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To map ganglion cell complex (GCC) thickness with high-speed Fourier-domain optical coherence tomography (FD-OCT) and compute novel macular parameters for glaucoma diagnosis. Design Observational, cross-sectional study. Participants One hundred seventy-eight participants in the Advanced Imaging for Glaucoma Study, divided into 3 groups: 65 persons in the normal group, 78 in the perimetric glaucoma group (PG), and 52 in the preperimetric glaucoma group (PPG). Methods The RTVue FD-OCT system was used to map the macula over a 7×6 mm region. The macular OCT images were exported for automatic segmentation using software we developed. The program measured macular retinal (MR) thickness and GCC thickness. The GCC was defined as the combination of nerve fiber, ganglion cell, and inner plexiform layers. Pattern analysis was applied to the GCC map and the diagnostic powers of pattern-based diagnostic parameters were investigated. Results were compared with time-domain (TD) Stratus OCT measurements of MR and circumpapillary nerve fiber layer (NFL) thickness. Main Outcome Measures Repeatability was assessed by intraclass correlation, pooled standard deviation, and coefficient of variation. Diagnostic power was assessed by the area under the receiver operator characteristic (AROC) curve. Measurements in the PG group were the primary measures of performance. Results The FD-OCT measurements of MR and GCC averages had significantly better repeatability than TD-OCT measurements of MR and NFL averages. The FD-OCT GCC average had significantly ( P = 0.02) higher diagnostic power (AROC = 0.90) than MR (AROC = 0.85 for both FD-OCT and TD-OCT) in differentiating between PG and normal. One GCC pattern parameter, global loss volume, had significantly higher AROC (0.92) than the overall average ( P = 0.01). The diagnostic powers of the best GCC parameters were statistically equal to TD-OCT NFL average. Conclusions The higher speed and resolution of FD-OCT improved the repeatability of macular imaging compared with standard TD-OCT. Ganglion cell mapping and pattern analysis improved diagnostic power. The improved diagnostic power of macular GCC imaging is on par with, and complementary to, peripapillary NFL imaging. Macular imaging with FD-OCT is a useful method for glaucoma diagnosis and has potential for tracking glaucoma progression. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Purpose To identify the best combination of Stratus optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness parameters for the detection of glaucoma. Design Observational cross-sectional study. Participants Eighty-nine age-matched normal and perimetric glaucoma participants enrolled in the Advanced Imaging for Glaucoma Study. Methods The Zeiss Stratus OCT system was used to obtain the circumpapillary RNFL thickness in both eyes of each participant. Right and left eye clock-hour data are analyzed together, assuming mirror-image symmetry. The RNFL diagnostic parameters were combined using either or-logic or and-logic approaches. Main Outcome Measures Area under the receiver operating characteristic curve (AROC), sensitivity, and specificity are used to evaluate diagnostic performance. Results Overall average RNFL thickness has the highest AROC value (0.89) of all single parameters evaluated, followed by the inferior and superior quadrants (0.88 and 0.86, respectively). The clock hours with the best AROC values are in the inferior and superior quadrants. The highest AROC (0.92) was achieved by the or-logic combination of overall, inferior, and superior quadrant RNFL thicknesses. The 3-parameter combination was significantly better than the overall average alone ( P = 0.01). The addition of more quadrants or clock hours to the combination reduced diagnostic performance. Conclusions The best stand-alone diagnostic strategy for Stratus OCT RNFL data is to classify an eye as glaucomatous if the overall, inferior quadrant, or superior quadrant RNFL thickness average is below normal.

Purpose To evaluate corneal opacities with optical coherence tomography (OCT). Design Prospective observational case series. Participants Twenty-three eyes of 19 patients with corneal opacities referred to a tertiary medical center. Methods Twenty-three consecutive eyes with corneal opacities were imaged with a high-speed corneal OCT prototype (Carl Zeiss Meditec, Inc., Dublin, CA). The OCT system operates at a speed of 2000 axial scans per second and a wavelength of 1.3 μm. Slit-scanning tomography (Orbscan II, software version 3.12; Bausch & Lomb, Inc., Rochester, NY) and ultrasound pachymetry (Corneo-Gage Plus; Sonogage, Cleveland, OH) also were performed. Main Outcome Measures Central cornea thickness was measured by the 3 instruments. Results In eyes with central opacities (n = 17), OCT central cornea thickness measurements were statistically equivalent to ultrasound pachymetry, whereas Orbscan II measurements were significantly less than ultrasound pachymetry (difference, −132.7±143 μm; P = 0.006). The OCT and ultrasound pachymetry results were obtained for all eyes, whereas Orbscan was unable to provide readings in 4 eyes. In eyes with off-center opacities (n = 6), OCT and Orbscan II central cornea thickness measurements were statistically equivalent to ultrasound pachymetry. The OCT measurements of epithelial thickness and scar depth also were demonstrated. Conclusions Optical coherence tomography provides consistent pachymetry mapping, whereas Orbscan II significantly underestimates corneal thickness in the presence of central corneal scars. Optical coherence tomography could be valuable in the planning of surgical treatment of corneal scars.

To map corneal thickness before and after LASIK with optical coherence tomography (OCT).Cross-sectional observational study.Forty-two eyes of 21 normal subjects undergoing LASIK.A high-speed (2000 axial scans/second) 1.3-microm-wavelength corneal and anterior segment OCT prototype was used for corneal scanning. The scan pattern consisted of 10-mm radial lines on 8 meridians centered on the vertex reflection. The entire scan pattern of 1024 a-scans was acquired in 0.5 seconds. We developed automated computer processing for 3-dimensional corneal reconstruction and measurement. Corneal thickness was measured normal to the anterior surface and presented as color pachymetry maps and zonal statistics. The maps were divided into a central zone (2 mm) and 3 annular areas (pericentral, 2-5 mm; transitional, 5-7 mm; peripheral, 7-10 mm), which were further divided into quadrantal zones. The average, minimum, and maximum corneal thicknesses were computed for zones within the 7-mm diameter. Optical coherence tomography and ultrasound pachymetry were measured 3 times at the preoperative and 3-month postoperative visits. Reproducibility was assessed by the pooled standard deviations (SDs) of the repeated measurements.Optical coherence tomography pachymetric map and zonal statistic, and ultrasound pachymetry.Before LASIK, central corneal thicknesses (CCTs) were 546.9+/-29.4 microm (mean +/- SD) for OCT and 553.3+/-33.0 microm for ultrasound. After LASIK, CCTs were 513.7+/-44.5 microm for OCT and 498+/-46.6 microm for ultrasound. Optical coherence tomography and ultrasound CCT were highly correlated (Pearson correlation r = 0.97 before LASIK and 0.98 afterwards). Optical coherence tomography CCT was slightly less than ultrasound CCT before surgery (mean difference, -6.4 microm; 95% limits of agreement, -23.2 to 10.4 microm) but slightly greater after LASIK (15.7 microm; -1.6 to 33 microm). These differences were statistically significant, but no more than the CCT measurement differences between ultrasound pachymeters. The reproducibility of the OCT zonal pachymetry averages was roughly 2 microm.High-speed OCT provided noncontact, rapid, reproducible pachymetric mapping over a wide area of the cornea. It is equivalent to ultrasound for CCT measurement before and after LASIK. This technology could be valuable for planning keratorefractive procedures and diagnosis of corneal diseases.

To describe LASIK for hyperopia, hyperopia with astigmatism, and mixed astigmatism and to examine the evidence to answer questions about the safety and efficacy of the procedure.A literature search conducted for the years 1968 to 2002 retrieved 118 citations. During review and preparation of this article, an additional 2 articles were included. The panel members selected 36 articles for the panel methodologist to review and rate according to the strength of evidence. A level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a level II rating to well-designed cohort and case-control studies; and a level III rating to case series, case reports, and poorly designed prospective and retrospective studies.This assessment describes 5 nonrandomized interventional trials (level II), 3 nonrandomized comparative trials (level III), and 20 noncomparative case series (level III). Additionally, 6 single-case reports (level III) were included because they reported relevant complications, and 2 theoretical analyses (level III) were also considered. This assessment does not compare studies because many variables such as range of hyperopia, follow-up periods, lasers, microkeratomes, techniques, and surgeon experience have not been controlled.For low (3 diopters [D]) to moderate (3-5 D) hyperopia, results from published studies (levels II and III evidence) have shown that LASIK is effective and predictable in achieving very good to excellent uncorrected visual acuity, achieving postoperative refractions within 1 D of emmetropia, and is safe in terms of minimal loss of best-corrected spectacle vision. Although there are fewer data for hyperopic astigmatism, the results available seem to mirror the data for low to moderate hyperopia (levels II and III evidence). The postoperative results for both uncorrected vision and safety are less compelling, as greater amounts of hyperopia are treated (4 to 5 D). Utilizing hyperopic LASIK for the treatment of consecutive hyperopia and astigmatism is also effective, although the ability to reduce hyperopic astigmatism after radial keratotomy is limited. Although a variety of ablation profiles can be used to treat mixed astigmatism, very good visual results have been reported (levels II and III evidence). Serious adverse complications leading to permanent visual loss are possible but, fortunately, very rare. There are insufficient data to compare one laser system with another or one ablation profile with another.

Objective To measure anterior chamber (AC) width and other dimensions relevant to the sizing of phakic intraocular lenses (IOLs) with a high-speed optical coherence tomography (OCT) system. Design Cross-sectional observational study. Participants Both eyes of 20 normal volunteers. Methods A novel high-speed (4000 axial scans/second) OCT prototype was developed for anterior segment scanning. The system uses long wavelength (1310 nm) for deeper angle penetration, rectangular scanning for undistorted imaging, and short image acquisition time (0.125 seconds) to reduce motion error. Three horizontal cross-sectional OCT images (15.5 mm wide and 6 mm deep) of the anterior segment were obtained from each eye with real-time image display to guide centration on the corneal apex. Image processing software was developed to correct for image warping resulting from index transitions. Anterior chamber dimensions were measured using computer calipers by 3 expert raters (ophthalmologists). Analysis of variance was used to determine interrater, interimage, right versus left eye, and intersubject standard deviation (SD) of OCT measurements. Main outcome measures Anterior chamber width (recess to recess), AC depth, and crystalline lens vault as measured by OCT; external white-to-white (WTW) corneal diameter (CD) as measured by Holladay-Godwin gauge. Results The mean AC width was 12.53±0.47 mm (intereye SD), and the mean corneal diameter was 11.78±0.57 mm. Optical coherence tomography measurement of AC width has good repeatability from image to image (SD, 0.134 mm), but there was significant difference between raters (SD, 0.215 mm). Estimation of AC width from WTW CD by linear regression was relatively inaccurate (residual SD, 0.41 mm). The mean AC depth was 2.99±0.323 mm (intereye SD), with repeatability of less than 0.001 mm (interimage SD), and the mean crystalline lens vault was 0.39±0.27 mm with 0.023 mm repeatability. Conclusions Reproducible OCT AC biometry was demonstrated using a high-speed OCT prototype. Further improvement in reproducibility may be achieved by automating the measurements with a computer. Direct OCT AC width measurement may improve sizing of angle-supported AC IOLs over conventional estimation by WTW CD. The measurement of AC depth and lens vault also may be useful for other types of phakic AC IOLs.

To assess corneal anatomic changes after LASIK with a high-speed corneal and anterior segment optical coherence tomography (CAS-OCT) system.Cross-sectional observational study.Fifty-one eyes of 26 healthy persons undergoing LASIK.The CAS-OCT prototype operated at a 1.3-mum wavelength and 2000 axial scans/second. The corneas were scanned with a flap profile pattern (horizontal line, 512 axial scans) and a flap map pattern (4 radials, 256 axial scans each). Both patterns are 8 mm long and are centered on the corneal vertex. LASIK flaps were created using either a mechanical microkeratome (Hansatome; BauschLomb, Inc., Rochester, NY) or a femtosecond laser (Pulsion; IntraLase Corp., Irvine, CA). Intraoperative pachymetry was performed using a 50-MHz ultrasound probe. Three OCT scans were obtained on preoperative and post-LASIK visits up to 6 months. An automated algorithm was developed to process the OCT images and to calculate corneal, flap, and stromal bed thickness profiles and maps. The profiles and maps were divided into central (diameter,2 mm), pericentral (2-5 mm), and transitional (5-7 mm) zones for analysis.Corneal, flap, and stromal bed thicknesses as determined by OCT and ultrasound pachymetry.The flap interface was best detected in the pericentral zone. One week after surgery, the repeatability of OCT flap and stromal bed thickness measurement was 2 to 7 microm by pooled standard deviation for zones inside a 5-mm diameter. The central flap thickness in 24 Hansatome eyes with a 180-microm setting was 143+/-14 microm by OCT and 131+/-17 microm by ultrasound. In the 8 IntraLase cases with a 120-microm setting, it was 156+/-11 microm by OCT and 160+/-19 microm by ultrasound. Eyes with other settings also were analyzed. There were small systematic changes in flap thickness up to 1 week and bed thickness up to 3 months.We have developed a method for using high-speed OCT to measure LASIK flap thickness after surgery. The measurement is noncontact, rapid, and repeatable. Profile and map measurements provide more information than point measurements previously demonstrated. This could be valuable for planning LASIK enhancement and characterizing microkeratome performance.