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Purpose To identify baseline risk factors for macular atrophy (MA) development in HARBOR via a longitudinal assessment of monthly spectral-domain (SD)-OCT scans. Previous analyses of MA in HARBOR examined data from color fundus photography (CFP) and fluorescein angiography (FA). Design Retrospective, post hoc analysis of SD-OCT images from HARBOR ( ClinicalTrials.gov identifier, NCT00891735 ), a phase 3, multicenter, prospective, randomized, double-blind, active treatment–controlled clinical trial. Participants Patients (N = 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with intravitreal ranibizumab 0.5 mg monthly (n = 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n = 275), 2.0 mg monthly (n = 274), or 2.0 mg PRN (n = 273). Methods Evaluable SD-OCT macular cube scans from patients with 24 months of follow-up (N = 941) were examined monthly from baseline to month 24 by masked reading center–trained graders. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, loss of retinal pigment epithelium, and loss of outer retinal layers. Multivariable proportional hazards regression was performed for time to atrophy development. Main Outcome Measures Risk factors for MA as determined by time to MA development over 24 months of treatment. Results Baseline risk factors for MA were confirmed from prior analyses that used CFP and FA data: absence of subretinal fluid, presence of intraretinal cysts, presence of Type 3 neovascularization, and presence of atrophy in the fellow eye. This analysis of SD-OCT data identified new baseline risk factors for MA: higher central drusen volume, lower choroidal thickness, presence of nascent atrophy, presence of reticular pseudodrusen, and increased central foveal thickness. Ranibizumab treatment regimen and dose level were not found to be risk factors for MA development. Conclusions In this analysis of a major nAMD trial using CAM atrophy criteria, new baseline risk factors for MA development were identified using an SD-OCT dataset. Risk factors for MA development identified by prior analyses were confirmed. Monthly treatment with ranibizumab 0.5 mg was not found to be a risk factor for MA development over 24 months.

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

Purpose Previous studies of macular atrophy (MA) in HARBOR analyzed color fundus photography and fluorescein angiography image data. This study performed a longitudinal assessment of monthly spectral-domain (SD) OCT scans to determine MA prevalence, incidence, and progression in HARBOR. Design Post hoc analysis of SD OCT images from HARBOR ( ClincalTrials.gov identifier, NCT00891735 ), a phase 3 multicenter, prospective, randomized, double-blind, active treatment–controlled clinical trial. Participants Patients (n = 1097) with subfoveal choroidal neovascularization secondary to neovascular age-related macular degeneration (nAMD) treated with ranibizumab 0.5 mg monthly (n = 275), 0.5 mg pro re nata (PRN) after 3 loading doses (n = 275), 2.0 mg monthly (n = 274), or 2.0 mg PRN (n = 273). Methods Evaluable SD OCT macular cube scans from patients with 24 months of follow-up (N = 941) were examined by masked reading center–trained graders monthly from baseline to month 24. Atrophy diagnosis criteria were consistent with those proposed by the Classification of Atrophy Meetings (CAM) group: hypertransmission of light into the choroid, retinal pigment epithelium loss, and loss of outer retinal layers. Macular atrophy was considered Definite if all 3 criteria were met and Questionable if 2 were met. Study arms were compared for time to MA detection (log-rank test) and enlargement rates (time × arm interaction test). Main Outcome Measures Prevalence, incidence, and enlargement rates of MA. Results At baseline, imbalance in MA rates across ranibizumab arms was evident (0.5 mg monthly, 19.1%; 0.5 mg PRN, 16.1%; 2.0 mg monthly, 10.1%; 2.0 mg PRN, 10.5%). At month 24, new MA development rates in eyes without baseline MA were similar between ranibizumab doses (0.5 mg, 25.9%; 2.0 mg, 25.4%) and treatment regimens (monthly, 26.4%; PRN, 25.0%). No significant differences in enlargement rate of new atrophy area (P = 0.479, square-root transformed) or time to detection of new MA (P = 0.997) were evident among study arms. Conclusions In this analysis of a major nAMD trial using CAM atrophy criteria, no differences were observed in incidence or progression rates of new MA among study arms, ranibizumab doses, or treatment regimens. Monthly versus PRN treatment did not influence MA incidence or progression.

Purpose The purpose of this study was to investigate the choroidal luminal and interstitial stromal alterations using choroidal vascularity index (CVI) among different cohorts of dry age-related macular degeneration (dAMD) compared to healthy subjects. Methods Four distinct cohorts were collected: three different cohorts of patients with dAMD (i.e. drusen, reticular pseudodrusen [RPD], and geographic atrophy [GA]) and an age-matched cohort of healthy subjects (controls). CVI (the ratio between the luminal choroidal area [LCA] and the total choroidal area [TCA]) was calculated in the subfoveal 1000 µm area. Results One hundred twenty eyes (from 120 patients) were included (30 eyes in each cohort). The mean age was 76.6 ± 7.1 years. No statistical differences were disclosed in terms of age, axial length, and central macular thickness among study groups. TCA showed a different distribution among the four cohorts (P = 0.003), mainly due to the LCA changes (P = 0.001). Interestingly, CVI showed a different distribution among the four cohorts (P < 0.001). RPD showed a lower CVI in comparison to controls (P = 0.040), whereas GA showed a lower CVI in comparison to drusen, RPD, and controls (P = 0.001, P = 0.046, and P < 0.001, respectively). Conclusions Different cohorts of dAMD are characterized by different impairments of the choroidal vascular and stromal components, reflecting different degrees of AMD severity. Translational Relevance CVI provides insights for better understanding the pathogenesis of AMD.

To investigate the choroidal vascularity index (CVI) in patients affected by leptochoroid.Three distinct age-matched cohorts were collected: patients with reticular pseudodrusen (RPD) secondary to age-related macular degeneration, patients with high-myopia, and healthy controls. CVI was calculated in the subfoveal 6000 μm diameter area.54 eyes (54 patients) were included (18 eyes in each cohort). No statistical differences were disclosed in terms of age between controls, RPD patients (p = 0.062), and myopic patients (p = 0.070). Total choroidal area showed a different distribution among the 3 cohorts (p 0.001), due to the reduction of luminal and stromal choroidal area in both RPD and myopic groups in comparison to controls (p 0.001). Interestingly, CVI showed a different distribution between the 3 cohorts (p 0.001). In detail, RPD group showed no changes in CVI in comparison to controls (p = 1.000), whereas the myopic group showed a higher CVI in comparison to both RPD group and controls (p 0.001 in both analyses).Different changes of the choroidal vascular and stromal components characterize the leptochoroid secondary to RPD eyes and high-myopic eyes. The relative greater impairment of the vascular area in RPD eyes in comparison to myopic eyes could be at the basis of the lower development of RPD in patients with high myopia.

Diabetic retinopathy screening is instrumental to preventing blindness, but scaling up screening is challenging because of the increasing number of patients with all forms of diabetes. We aimed to create a deep-learning system to predict the risk of patients with diabetes developing diabetic retinopathy within 2 years.We created and validated two versions of a deep-learning system to predict the development of diabetic retinopathy in patients with diabetes who had had teleretinal diabetic retinopathy screening in a primary care setting. The input for the two versions was either a set of three-field or one-field colour fundus photographs. Of the 575 431 eyes in the development set 28 899 had known outcomes, with the remaining 546 532 eyes used to augment the training process via multitask learning. Validation was done on one eye (selected at random) per patient from two datasets: an internal validation (from EyePACS, a teleretinal screening service in the USA) set of 3678 eyes with known outcomes and an external validation (from Thailand) set of 2345 eyes with known outcomes.The three-field deep-learning system had an area under the receiver operating characteristic curve (AUC) of 0·79 (95% CI 0·77-0·81) in the internal validation set. Assessment of the external validation set-which contained only one-field colour fundus photographs-with the one-field deep-learning system gave an AUC of 0·70 (0·67-0·74). In the internal validation set, the AUC of available risk factors was 0·72 (0·68-0·76), which improved to 0·81 (0·77-0·84) after combining the deep-learning system with these risk factors (p0·0001). In the external validation set, the corresponding AUC improved from 0·62 (0·58-0·66) to 0·71 (0·68-0·75; p0·0001) following the addition of the deep-learning system to available risk factors.The deep-learning systems predicted diabetic retinopathy development using colour fundus photographs, and the systems were independent of and more informative than available risk factors. Such a risk stratification tool might help to optimise screening intervals to reduce costs while improving vision-related outcomes.Google.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Purpose To investigate the effect of multiple enface image averaging on image quality of the optical coherence tomography angiography (OCTA). Methods Twenty-one normal volunteers were enrolled in this study. For each subject, one eye was imaged with 3 × 3 mm scan protocol, and another eye was imaged with the 6 × 6 mm scan protocol centred on the fovea using the ZEISS Angioplex™ spectral-domain OCTA device. Eyes were repeatedly imaged to obtain nine OCTA cube scan sets, and nine superficial capillary plexus (SCP) and deep capillary plexus (DCP) were individually averaged after registration. Results Eighteen eyes with a 3 × 3 mm scan field and 14 eyes with a 6 × 6 mm scan field were studied. Averaged images showed more continuous vessels and less background noise in both the SCP and the DCP as the number of frames used for averaging increased, with both 3 × 3 and 6 × 6 mm scan protocols. The intensity histogram of the vessels dramatically changed after averaging. Contrast-to-noise ratio (CNR) and subjectively assessed image quality scores also increased as the number of frames used for averaging increased in all image types. However, the additional benefit in quality diminished when averaging more than five frames. Averaging only three frames achieved significant improvement in CNR and the score assigned by certified grades. Conclusion Use of multiple image averaging in OCTA enface images was found to be both objectively and subjectively effective for enhancing image quality. These findings may of value for developing optimal OCTA imaging protocols for future studies.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. In this study, we compare the performance of retinal fundus images and genetic-information-based machine learning models for the prediction of late AMD. Using data from the Age-related Eye Disease Study, we built machine learning models with various combinations of genetic, socio-demographic/clinical, and retinal image data to predict late AMD using its severity and category in a single visit, in 2, 5, and 10 years. We compared their performance in sensitivity, specificity, accuracy, and unweighted kappa. The 2-year model based on retinal image and socio-demographic (S-D) parameters achieved a sensitivity of 91.34%, specificity of 84.49% while the same for genetic and S-D-parameters-based model was 79.79% and 66.84%. For the 5-year model, the retinal image and S-D-parameters-based model also outperformed the genetic and S-D parameters-based model. The two 10-year models achieved similar sensitivities of 74.24% and 75.79%, respectively, but the retinal image and S-D-parameters-based model was otherwise superior. The retinal-image-based models were not further improved by adding genetic data. Retinal imaging and S-D data can build an excellent machine learning predictor of developing late AMD over 2–5 years, the retinal imaging model appears to be the preferred prognostic tool for efficient patient management.

Purpose To evaluate retinal vascular status during pregnancy by using optical coherence tomography angiography (OCTA). Methods Women in their third trimester of pregnancy and nonpregnant age-matched women were recruited for this prospective, case-control study. Subjects were imaged with OCTA. Main outcome measures were foveal avascular zone parameters, perfusion density (PD) percentage in the superficial retinal capillary plexus (SCP), PD percentage in the deep retinal capillary plexus (DCP), SCP vessel length density (VLD), DCP-VLD, and choriocapillaris (CC) flow voids (i.e., flow deficits in the CC). Results Nineteen eyes of 10 pregnant subjects and 44 eyes of 27 nonpregnant control women were included. Mean ages were 36 ± 7 and 35 ± 8 years (SD), respectively (P value = 0.78). Mean gestational age of pregnant women was 33 weeks (range = 29-39, SD = 3). There was a significant reduction in the SCP-PD in the entire scan and in the nasal Early Treatment Diabetic Retinopathy Study subfield (47.9 vs. 49.7, P = 0.04 and 49.3 vs. 51.6, P = 0.03, respectively) in the pregnant cohort versus controls. There was a significant increase in the DCP-PD in the parafoveal region and in the temporal and inferior Early Treatment Diabetic Retinopathy Study subfields (58.0 vs. 55.9, P = 0.03; 57.9 vs. 55.5, P = 0.02; 58.0 vs. 55.9, P = 0.05, respectively) in the pregnant cohort. There was no significant difference in foveal avascular zone parameters, SCP-VLD, DCP-VLD, or CC flow voids between the two populations. Conclusions This study detected retinal vasculature changes in the third trimester of pregnancy. Mean SCP-PD was significantly decreased and mean DCP-PD was significantly increased without a difference in VLD.

Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging.To investigate multiple en face image averaging on OCTA images of the choriocapillaris.Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016.All participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images.Vessel caliber measurement.Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images.Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.

Purpose The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Methods Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. Results A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Conclusion Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These observations suggest that choroidal parameters beyond thickness warrant further study in the setting of age-related macular degeneration.

Importance The repeatability and reproducibility of quantitative metrics from optical coherence tomographic angiography (OCTA) must be assessed before these data can be confidently interpreted in clinical research and practice. Objective To evaluate the repeatability and reproducibility of OCTA-derived retinal vascular quantitative metrics. Design, Setting and Participants In this cross-sectional study, 21 healthy volunteers (42 eyes) and 22 patients with retinal disease (22 eyes), including 14 with age-related macular degeneration, 3 with epiretinal membrane, 2 with diabetic retinopathy, 2 with myopic macular degeneration, and 1 with retinal vein occlusion, were enrolled. Participants were recruited from September 1 through November 31, 2016. Each eye underwent 3 repeated scans with 3 instruments for a total of 9 acquisitions. Eyes were randomly assigned to scanning with a 3 × 3-mm or 6 × 6-mm pattern. Eyes were excluded from subsequent analysis if any acquisition had a signal strength of less than 7. Repeatability (defined as the agreement in measurements within a device) and reproducibility (defined as the agreement between devices of the same type) were assessed by intraclass correlation coefficient (ICC) and coefficient of variation. Exposures All eyes underwent scanning using 3 separate devices. Main Outcomes and Measures Vessel length density (VLD) and perfusion density (PD) of the superficial retinal vasculature. Results A total of 21 healthy volunteers (8 men and 13 women; mean [SD] age, 36 [6] years) and 22 patients with retinal disease (15 men and 7 women; mean [SD] age, 79 [9] years) underwent evaluation. Of these, 40 of 42 normal eyes and 15 of 22 eyes with retinal disease met signal strength criteria and were included in this analysis. The ICC among the 3 consecutive scans ranged from 0.82 to 0.98 for VLD and from 0.83 to 0.95 for PD. The coefficient of variation (CV) ranged from 2.2% to 5.9% for VLD and from 2.4% to 5.9% for PD. For reproducibility, the ICC ranged from 0.62 to 0.95 and the CV was less than 6% in all groups. The agreement was highest for the 3 × 3-mm pattern in the inner ring (ICC range, 0.92 [95% CI, 0.85-0.96] to 0.96 [95% CI, 0.93-0.98]) and 6 × 6-mm pattern in the outer ring (ICC range, 0.93 [95% CI, 0.86-0.97] to 0.96 [95% CI, 0.92-0.98]). Conclusions and Relevance Vessel length density and PD of the superficial retinal vasculature can be obtained from OCTA images with high levels of repeatability and reproducibility but can vary with scan pattern and location.

Purpose To investigate the level of inaccuracy of retinal thickness measurements in tilted and axially stretched optical coherence tomography (OCT) images. Methods A consecutive series of 50 eyes of 50 patients with age-related macular degeneration were included in this study, and Cirrus HD-OCT images through the foveal center were used for the analysis. The foveal thickness was measured in three ways: (1) parallel to the orientation of the A-scan (Tx), (2) perpendicular to the retinal pigment epithelium (RPE) surface in the instrument-displayed aspect ratio image (Ty), and (3) thickness measured perpendicular to the RPE surface in a native aspect ratio image (Tz). Mathematical modeling was performed to estimate the measurement error. Results The measurement error was larger in tilted images with a greater angle of tilt. In the simulation, with axial stretching by a factor of 2, Ty/Tz ratio was > 1.05 at a tilt angle between 13° to 18° and 72° to 77°, > 1.10 at a tilt angle between 19° to 31° and 59° to 71°, and > 1.20 at an angle ranging from 32° to 58°. Of note with even more axial stretching, the Ty/Tz ratio is even larger. Tx/Tz ratio was smaller than the Ty/Tz ratio at angles ranging from 0° to 54°. The actual patient data showed good agreement with the simulation. The Ty/Tz ratio was greater than 1.05 (5% error) at angles ranging from 13° to 18° and 72° to 77°, greater than 1.10 (10% error) angles ranging from 19° to 31° and 59° to 71°, and greater than 1.20 (20% error) angles ranging from 32° to 58° in the images axially stretched by a factor of 2 (b/a = 2), which is typical of most OCT instrument displays. Conclusions Retinal thickness measurements obtained perpendicular to the RPE surface were overestimated when using tilted and axially stretched OCT images. Translational relevance If accurate measurements are to be obtained, images with a native aspect ratio similar to microscopy must be used.

The electrochemical oxidation of carbon monoxide adsorbed (COad) on platinum-on-carbon electrodes was studied via a methodology in which pre-adsorbed CO was partially oxidized by applying potentiostatic pulses for certain durations. The residual COad was analyzed using stripping voltammetry that involved the deconvolution of COad oxidation peaks of voltammograms to quantify the weakly and strongly bound species of COad. The data obtained for various potentials and temperatures were fit to a model based on a nucleation and growth mechanism. The resulting fit produced potential- and temperature-dependent rate parameters that provided insight into the oxidation mechanism of the two COad species. Irrespective of the applied potential or temperature, the concentration of weakly bound COad species decreased exponentially with time. In contrast, the strongly bound COad species showed a gradual transition of mechanisms, from progressive nucleation at relatively low potentials to exponential decay at high potentials., Comment: 15 pages, 9 figures

Purpose Keratoconus is a degenerating disease of the eye which causes an irregularly shaped cornea leading to impairment of vision.The role of proteases in keratoconus has been a topic of substantial discussion and speculation over many years.This study was designed to examine the levels and activity of proteases in the tear film of people with keratoconus. Methods A case-controlled study was performed studying the tear proteome of keratoconus patients(K) and controls(N).Basal tears were collected using a capillary tube.Total protein(TP)in tears was estimated using BCA assay;the levels of lactoferrin(Lf),secretory immunoglobin A(sIgA) and serum albumin were measured using specific ELISAs.Levels and activity of tear proteases were studied using Raybiotech® Antibody Array and EnzChek® Assay Kits respectively. Results There was a two-fold (p=0.0001) decrease in TP levels between K(3.86+1.62 mg/ml) and N(7.00+1.58 mg/ml). Levels of Lf(0.67+0.28 vs. 1.13+0.29 mg/ml) and sIgA(0.78+0.36 vs. 1.70+0.66 mg/ml) were also significantly(p=0.0001) reduced in K. The expression levels of matrix metalloproteinases(MMP)-1,-2,-3,-7,-13,interleukins(IL)-1α,-3,-4,-5,-6,-8,-10 and tumour necrosis factor(TNF)-α,-β were significantly(p=0.01)altered between K and N. Tear proteolysis(gelatinase/collagenase)was expressed as Fluorescence Intensity(FI).The activity of gelatinases(87.54+33.57 vs. 45.79+24.60 FI,p=0.0002)and collagenases(6.11+3.18 vs. 3.56+2.03 FI,p=0.03)were significantly increased in K. Conclusion The tears of people with keratoconus expressed high levels of proteases, increased proteolysis and a profoundly altered protein profile, which might change with the severity of the disease.These findings may lead the way to understanding or monitoring disease progression.