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Objective To describe optical coherence tomography angiography (OCTA) reflectance artifacts secondary to retinal pigment epithelial detachment (RPED). Design Retrospective review. Methods Four eyes from 4 subjects were included. Three presented with RPED and 1 eye was a normal control. Two eyes diagnosed with RPED and the normal eye were evaluated using en face OCTA centred at the fovea acquired using the RTVue XR Avanti (Optovue Inc). In the third eye with RPED, OCTA imaging was performed using a CIRRUS 5000 prototype modified to do OCTA imaging on a spectral domain OCT platform provided by Carl Zeiss Meditec, Inc. The segmented OCTA angiograms were overlaid to determine if the flow patterns seen at the edge of the RPEDs were due to reflectance from the inner retinal vessels, also known as “decorrelation tails.” Results OCTA projection artifacts were noted when segmentation lines intersected with the boundary of the RPED. The overlaid segmented OCTA from the 3 RPED eyes imaged using each system revealed the same vasculature pattern at the edges of the RPED as that of the inner retina, demonstrating the “decorrelation tails” artifact, which caused the RPED to appear as a bright ring on the segmented OCTA. Conclusions OCTA images are susceptible to various known artifacts. This series describes the impact of the projection artifact seen at the edges of an RPED that simulates appearance of flow but is actually due to reflectance of the inner retinal vasculature on the RPED.

Background To evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES). Methods In vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit’s eyes following injection. Results Eighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 µL/mL LES). 92.95% in group 2 (25 µL/mL LES), 91.59% in group 3 (50 µL/mL LES), 98.09% in group 4 (12.5 µL/mL EL), 95.20% on group 5 (50 µL/mL EL), 98.53% in group 6 (50 µL/mL EL), and 2.84% on group 8 (50 µL/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p = 1.0), but the comparison of all groups with group 8 was significant (p Conclusion A novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.

To describe qualitative and quantitative optical coherence tomography (OCT) angiography (OCTA) parameters for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and their applicability as potential clinical trial endpoints.A review of current literature related to the topic of OCTA and AMD.There are a number of promising OCTA parameters that can be used to diagnose the presence of CNV and to monitor the activity and progression of the lesion, pre- and post-treatment morphological characteristics, CNV dimensions, and automated quantitative parameters such as vessel density.The OCTA parameters described in this review have promise for the future development of clinical trial endpoints, but require further validation before they can be widely used.

Purpose To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultrahigh-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype vs a spectral-domain (SD) OCTA device. Design Comparative analysis of diagnostic instruments. Methods Patients were prospectively recruited to be imaged on SD OCT and SS OCT devices on the same day. The SD OCT device employed is the RTVue Avanti (Optovue, Inc, Fremont, California, USA), which operates at ∼840 nm wavelength and 70 000 A-scans/second. The SS OCT device used is an ultrahigh-speed long-wavelength prototype that operates at ∼1050 nm wavelength and 400 000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the 2 devices. The nonparametric Wilcoxon signed rank test was used to compare area measurements and P values of, National Institutes of Health (U.S.) (R01-EY011289-28), National Institutes of Health (U.S.) (R44-EY022864-03), National Institutes of Health (U.S.) (R01-CA075289-17), United States. Air Force Office of Scientific Research (FA9550-10-1-0551), United States. Air Force Office of Scientific Research (FA9550-12-1-0499)

Optical coherence tomography angiography (OCTA) is a noninvasive, rapid imaging technique that generates angiographic images without intravenous dye injections. Cross-sectional studies have described the presence of asymptomatic choroidal neovascularization (CNV) in patients with intermediate age-related macular degeneration (AMD). This case report describes the OCT features on longitudinal follow-up of a patient who started with unilateral asymptomatic CNV and eventually developed symptomatic exudative AMD. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:596–598. ]

To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex.Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements.No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions.There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.

PURPOSE To compare foveal vascular anatomy between patients with and without disorganization of retinal inner layers (DRILs) after resolved diabetic macular edema using optical coherence tomography angiography (OCTA). METHODS Twenty-four eyes of 21 age- and sex-matched patients with resolved diabetic macular edema were included in this retrospective, cross-sectional study. All eyes were imaged with enhanced high-definition line or cross-line structural B scans and 3 × 3-mm OCTA scans. Optical coherence tomography B scans were analyzed for the presence of DRIL, and based on this, eyes were classified as either DRIL present or DRIL absent. The foveal avascular zone area on OCTA was compared between patients with and without DRIL. The foveal avascular zone area was correlated with visual acuity. RESULTS Nine eyes with DRIL and resolved diabetic macular edema were compared with 15 control eyes without DRIL and resolved diabetic macular edema. Area of ischemia on OCTA scans corresponded to the area of DRIL as determined on OCT B scans. The foveal avascular zone area in full retina as well as superficial and deep retinal plexuses OCTA slabs were significantly larger in patients with DRIL as compared to those without DRIL (P = 0.005, P < 0.001, and P = 0.004, respectively). The larger foveal avascular zone in full retinal segmentation (r = 0.72, P = 0.03) and superficial plexus (r = 0.74, P = 0.02) were positively correlated with lower visual acuity. CONCLUSION Optical coherence tomography angiography can visualize retinal ischemia in patients with and without DRIL. Correspondence of impaired blood flow with DRIL suggests that retinal ischemia and loss of normal vasculature contributes to DRIL.

PURPOSE: To examine the definition, rationale, and effects of thresholding in OCT angiography (OCTA). DESIGN: A theoretical description of OCTA thresholding in combination with qualitative and quantitative analysis of the effects of OCTA thresholding in eyes from a retrospective case series. PARTICIPANTS: Four eyes were qualitatively examined: 1 from a 27-year-old control, 1 from a 78-year-old exudative age-related macular degeneration (AMD) patient, 1 from a 58-year-old myopic patient, and 1 from a 77-year-old nonexudative AMD patient with geographic atrophy (GA). One eye from a 75-year-old nonexudative AMD patient with GA was quantitatively analyzed. MAIN OUTCOME MEASURES: A theoretical thresholding model and a qualitative and quantitative description of the dependency of OCTA on thresholding level. RESULTS: Due to the presence of system noise, OCTA thresholding is a necessary step in forming OCTA images; however, thresholding can complicate the relationship between blood flow and OCTA signal. CONCLUSIONS: Thresholding in OCTA can cause significant artifacts, which should be considered when interpreting and quantifying OCTA images., Macula Vision Research Foundation, National Institutes of Health (U.S.) (NIH R01-EY011289-29A), National Institutes of Health (U.S.) (R44-EY022864), National Institutes of Health (U.S.) (R01-CA075289-16), United States. Air Force. Office of Scientific Research (AFOSR FA9550-15-1-0473), United States. Air Force. Office of Scientific Research (FA9550-12-1-0499), Praevium Research Inc., Massachusetts Lions Clubs, Samsung (Firm) (Scholarship)

Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) is a rare syndrome affecting the retinal and optic disc vasculature. Diffuse retinal ischemia, macular edema, and neovascularization may lead to bilateral vision loss. The authors report a case of a 36-year-old woman presenting with branch retinal artery occlusion (BRAO) in her right eye who was subsequently diagnosed with IRVAN syndrome. She was treated with panretinal photocoagulation for peripheral retinal ischemia and pars plana vitrectomy for vitreous hemorrhage. She later developed a BRAO in her left eye. This case demonstrates that BRAO may be a presenting feature of IRVAN syndrome. [ Ophthalmic Surg Lasers Imaging Retina . 2017;48:948–951.]

PURPOSE To illustrate errors in the automated segmentation image analysis of optical coherence tomography angiography after laser photocoagulation therapy for Type 2 neovascularization. METHODS This case report describes a patient with extrafoveal Type 2 neovascularization treated with argon laser photocoagulation evaluated before and after treatment by optical coherence tomography angiography. RESULTS Disrupted retinal layers after laser photocoagulation therapy lead to segmentation errors. CONCLUSION Images of optical coherence tomography angiography are prone to degradation by artifacts in cases in which there is disruption of the retinal layers. Clinicians must be aware of these errors because they can be misinterpreted as active Type 2 neovascularization. Improvement in optical coherence tomography angiography image analysis to minimize automated segmentation errors needs to be further explored.

Purpose: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). Methods: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. Results: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. Conclusion: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials., National Institutes of Health (U.S.) (Grants NIH R01-EY011289-29A, R44-EY022864, R01-CA075289-16, FA9550-15-1-0473 and FA9550-12-1-0499)

To describe the appearance of a scleral-derived feeder vessel in a highly myopic eye with secondary choroidal neovascularization (CNV) as visualized on both en face high-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype, and a commercially available spectral-domain (SD) OCTA, with the corresponding en face and cross-sectional structural OCT images. In this case report, a 60-year-old white male presented with high myopia and secondary CNV in the right eye, previously treated with anti-vascular endothelial growth factor, and was imaged on both SD-OCT and SS-OCT. The neovascular complex could be visualized on both devices. Structural en face SS-OCT images demonstrated a large choroidal-scleral feeder vessel that was not visualized with SD-OCT. The authors concluded that structural en face SS-OCT better visualizes scleral feeder vessel compared to SD-OCT due to the longer wavelength (∼1,050 nm) with increased choroidal penetration and decreased sensitivity roll-off in the SS-OCT system. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:960–964.]

Background To investigate the choroidal thickness in older patients with central serous chorioretinopathy (CSCR) compared to age-matched normal subjects. Methods Fifteen patients (30 eyes) with CSCR, all aged ≥60 years, and 21 age-matched normal subjects (21 eyes) underwent high-definition raster scanning using SD-OCT. Both eyes from CSCR patients were included in the analysis. The eyes in patients with CSCR were divided into two groups: active CSCR (17 eyes) if there was foveal-involving subretinal fluid and inactive contralateral eye group (13 eyes). Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroidal–scleral junction at 500 µm intervals up to 2500 µm temporal and nasal to the fovea (11 locations). Results The mean age of the patients with CSCR was 68.87 ± 6.83 years (mean ± standard deviation). Reliable measurements of choroidal thickness were obtainable in 70.6 % of eyes examined. The choroid was statistically significantly thicker in eyes with both active CSCR (P 0.05). Conclusion Choroid in older patients with active CSCR was thicker than the choroid in age-matched normal eyes. It is important to consider CSCR as a differential diagnosis of serous retinal detachment in elderly patients with thickened choroid and to consider SD-OCT as an imaging modality by which to evaluate the choroidal thickness.

Purpose: To evaluate the perifoveolar retinal capillary network at different depths and to quantify the foveal avascular zone (FAZ) in eyes with retinal vein occlusion (RVO) compared with their fellow eyes and healthy controls using spectral-domain optical coherence tomography angiography (SD-OCTA). Methods: We prospectively recruited 23 patients with RVO including 15 eyes with central RVO (CRVO) and 8 eyes with branch RVO (BRVO), their fellow eyes, and 8 age-matched healthy controls (8 eyes) for imaging on prototype OCTA software within RTVue-XR Avanti. The 3 × 3 mm and 6 × 6 mm en face angiograms of superficial and deep retinal capillary plexuses were segmented. Perifoveolar retinal capillary network was analyzed and FAZ was quantified. Results: Decrease in vascular perfusion at the deep plexus was observed in all eyes with CRVO (8/8, 100%) and BRVO (6/6, 100%) without cystoid macular edema, and in 8 of 15 (53%) and 2 of 8 (25%) of the fellow eyes, respectively. Vascular tortuosity was observed in 13 of 15 (87%) CRVO and 5 of 8 (63%) BRVO eyes. Collaterals were seen in 10 of 15 (67%) CRVO and 5 of 8 (63%) BRVO eyes. Mean FAZ area was larger in eyes with RVO than their fellow eyes (1.13 ± 0.25 mm[superscript 2] versus 0.58 ± 0.28 mm[superscript 2]; P = 0.007) and controls (1.13 ± 0.25 mm[superscript 2] versus 0.30 ± 0.09 mm[superscript 2]; P < 0.0001), and in fellow eyes of RVO patients when compared to controls (0.58 ± 0.28 mm[superscript 2] versus 0.30 ± 0.09 mm[superscript 2]; P = 0.01). Conclusions: Spectral-domain OCTA reveals abnormalities at different levels of perifoveolar retinal capillary network and is able to quantify the FAZ in RVO. Longitudinal studies may be considered to evaluate the clinical utility of OCTA in RVO and other retinal vascular diseases., Massachusetts Lions Eye Research Fund, Inc., Brazil. Ministry of Education

Purpose. To compare fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) images of foveal avascular zone (FAZ) in patients with diabetic retinopathy (DR) with and without diabetic macular ischemia (DMI).Methods. The Wilcoxon signed-rank test was used to compare area measurements andpvalues of 2) and “small” (inferior to 0.32 mm2) groups. Quantitative analyses of the FAZ were performed using custom software.Results. Thirty-four eyes from 34 diabetic patients were enrolled. Subjects with DMI presented a mean area on FA and OCTA of 0.68 ± 0.53 mm2and 0.58 ± 0.35 mm2, respectively (p=0.1374). Patients without DMI presented a mean area on FA and OCTA of 0.19 ± 0.67 mm2and 0.20 ± 0.79 mm2, respectively (p=0.9594). The ICC for the FAZ measurements between the 2 observers on FA and OCTA was 0.96 and 0.92, respectively.Conclusion. OCTA represents a novel technique for the diagnosis of DMI and it may become an alternative to FA for this purpose.

BACKGROUND AND OBJECTIVE: To compare the visualization of microaneurysms (MA) and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) versus fluorescein angiography (FA) in patients with diabetic macular edema (DME). PATIENTS AND METHODS: Patients were prospectively recruited for same-day imaging on spectral-domain OCTA and FA. OCTA images were automatically segmented into superficial (sOCTA) and deep (dOCTA) capillary plexuses. The number of visible MAs and the FAZ area were compared between the two imaging modalities. RESULTS: Nineteen eyes of 10 patients were included. There was a statistically significant difference between MA counts for FA, sOCTA, and dOCTA ( P = .002), and median MA counts were 14.5 (range: 2–43), 9.75 (range: 0–37.5), and 22.5 (range: 5.5–46.5), respectively. dOCTA showed significantly more MAs than sOCTA ( P < .001). Although not significant statistically, dOCTA revealed more MAs than FA ( P = .06). There was a statistically significant difference between FAZ area for FA, sOCTA, and dOCTA ( P = .046), and median FAZ areas were 0.444 (range: 0.1–0.689), 0.224 (range: 0.335–0.806), and 0.345 (range: 0.106–0.881), respectively. FA showed a significantly larger FAZ area than sOCTA ( P = .04). CONCLUSIONS: Deep plexus OCTA can better identify microaneurysms compared to either sOCTA or FA. The FAZ area appears larger on FA in contrast to OCTA of both plexuses. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:1013–1019.]

Fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been the gold standard for the evaluation of retinal and choroidal vasculature in the last three decades and have revolutionized the diagnosis of retinal and choroidal vascular diseases. The advantage of these imaging modalities lies in their ability to document retinal and choroidal vasculature through the dynamic assessment of contrast transit over time in the intravascular and extravascular spaces. However, disadvantages include the absence of depth resolution, blurring of details by contrast leakage, and the inability to selectively evaluate different levels of the retinal and choroidal microvasculature. In addition, these angiographic methods require intravenous dye, which may cause adverse reactions such as nausea, vomiting, and rarely, anaphylaxis. Optical coherence tomography angiography (OCTA) is a noninvasive imaging technique that, in contrast to dye-based angiography, is faster and depth-resolved, allowing in some cases for more precise evaluation of the vascular plexuses of the retina and choroid. The method has been demonstrated in the assessment of various vascular diseases such as venous occlusions, diabetic retinopathy, macular neovascularization, and others. Limitations of this imaging modality include a small registered field of view and the inability to visualize leakage and dye transit over time. It is also subject to a variety of artifacts, including those generated by blinking and eye movement during image acquisition. However, more than an alternative for FA and ICGA, OCTA is bringing new insights to our understanding of retinal and choroidal vascular structure and is changing fundamental paradigms in the clinical management of pathologic conditions. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:848–861.]

PURPOSE: To describe pachymetric progression indices (PPI) of the Pentacam HR (Oculus Optikgeräte GmbH) and the concept of relational thickness, and to test their accuracy for differentiating keratoconic and normal corneas compared with single-point thickness values. METHODS: One hundred thirteen individual eyes randomly selected from 113 normal patients and 44 eyes of 44 patients with keratoconus were studied using the Pentacam HR by acquiring central corneal thickness (CCT), thinnest point (TP), position of the TP and PPI at minimal (PPI Min) and maximal (PPI Max) meridians, and the average (PPI Ave) of all meridians. Relational thickness parameters were calculated as the ratios of TP and CCT and PPI values. Mann-Whitney U test assessed differences in groups for each variable. Receiver operating characteristic (ROC) curves were calculated for all variables and pairwise comparisons were performed. RESULTS: Statistically significant differences were noted between normal and keratoconic eyes for all parameters ( P P =.79). The best parameters, named Ambrósio’s Relational Thickness (ART), were ART-Ave (TP/PPI Ave) and ART-Max (TP/PPI Max) with areas under the ROC curves of 0.987 and 0.983, respectively. The best cutoffs were 424 μm and 339 μm for ART-Ave and ART-Max, respectively. Pachymetric progression indices and ART had a greater area under the curve than TP and CCT ( P P =.002). CONCLUSIONS: Tomographic-derived pachymetric parameters were better able to differentiate normal and keratoconic corneas than single-point pachymetric measurements. Further studies are needed to evaluate the role of tomography in identifing early forms of ectasia as well as ectasia risk among LASIK candidates.

Purpose: To use a novel optical coherence tomography angiography (OCTA) algorithm termed variable interscan time analysis (VISTA) to evaluate relative blood flow speeds in polypoidal choroidal vasculopathy (PCV). Methods: Prospective cross-sectional study enrolling patients with confirmed diagnosis of PCV. OCTA of the retina and choroid was obtained with a prototype swept-source OCT system. The acquired OCT volumes were centered on the branching vascular network (BVN) and polyps as determined by indocyanine-green angiography (ICGA). The relative blood flow speeds were characterized on VISTAOCTA. Results: Seven eyes from seven patients were evaluated. Swept-source OCTA enabled detailed enface visualization of the BVN and polyps in six eyes. VISTA-OCTA revealed variable blood flow speeds in different PCV lesion components of the same eye, with faster flow in the periphery of polyps and slower flow in the center of each polyp, as well as relatively slow flow in BVN when compared with retinal vessels. BVNs demonstrated relatively faster blood flow speeds in the larger trunk vessels and relatively slower speeds in the smaller vessels. Conclusions: Swept-source OCTA identifies polyps in most, but not all, PCV lesions. This limitation that may be related to relatively slow blood flow within the polyp, which may be below the OCTA’s sensitivity. VISTA-OCTA showed heterogeneous blood flow speeds within the polyps, which may indicate turbulent flow in the polyps. Translational Relevance: These results bring relevant insights into disease mechanisms that can account for the variable course of PCV, and can be relevant for diagnosis and management of patients with PCV. Keywords: OCTA; optical coherence tomography angiography; PCV; polypoidal choroidal vasculopathy; variable interscan time analysis, National Institutes of Health (U.S.) (Grant R01-EY011289-29A), National Institutes of Health (U.S.) (Grant R44- EY022864), National Institutes of Health (U.S.) (Grant R01-CA075289-16), Air Force Office of Scientific Research (Grant FA9550-15-1-0473), Air Force Office of Scientific Research (Grant FA9550-12-1-0499)

Purpose: To utilize optical coherence tomography (OCT) and OCT angiography (OCTA) to describe alterations in the retinal and choriocapillaris vasculature following remote laser photocoagulation. Lesions are classified on the basis of choriocapillaris alteration as evaluated on en face OCTA. Methods: This was a retrospective, cross-sectional study analyzing 28 laser photocoagulation scars from 8 patients treated for diabetic macular edema. All eyes were analyzed using a combination of OCTA, en face and cross-sectional OCT, and fundus photography. Two masked readers scored images for alterations at the level of the retinal pigment epithelium (RPE), choroid, and choriocapillaris. Laser photocoagulation lesions were classified as deep if choriocapillaris alteration was present on OCTA; lesions were classified as superficial if no choriocapillaris alteration was present on OCTA. Results: Optical coherence tomography angiography was found to be useful for evaluation of choriocapillaris alteration underlying regions of laser scarring. Of the 28 analyzed laser scars, 13 were classified as superficial and 15 were classified as deep. Conclusions: Optical coherence tomography angiography can be used to visualize choriocapillaris alterations associated with focal laser photocoagulation treatment., Massachusetts Lions Eye Research Fund, Inc., Macular Vision Research Foundation