Artificial intelligence-aided diagnosis and treatment in the field of optometry.

With the rapid development of computer technology, the application of artificial intelligence (AI) to ophthalmology has gained prominence in modern medicine. As modern optometry is closely related to ophthalmology, AI research on optometry has also increased. This review summarizes current AI research and technologies used for diagnosis in optometry, related to myopia, strabismus, amblyopia, optical glasses, contact lenses, and other aspects. The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

COMPARISON OF PROJECTION-RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY-BASED METRICS FOR THE EARLY DETECTION OF RETINAL MICROVASCULAR IMPAIRMENTS IN DIABETES MELLITUS.

PURPOSE: To determine the ability of nonperfusion, vessel density, and morphologic measurements using projection-resolved optical coherence tomography angiography to detect early retinal microvasculature impairments in diabetes mellitus. METHODS: A retrospective review was performed on Type 2 diabetes mellitus patients with no diabetic retinopathy (DR) or mild nonproliferative DR and age-matched controls imaged with optical coherence tomography angiography. Foveal avascular zone-related metrics and extrafoveal avascular area were measured in optical coherence tomography angiography images. Vessel density and fractal dimension were calculated with and without a skeletonization process. The vessel diameter index and vessel tortuosity were computed. The area under the receiver operating characteristic curve (AUC) estimated diagnostic performances. RESULTS: Dilated capillary diameter was observed in the deep capillary plexus in the diabetic groups. Vessel density and fractal dimension of skeletonized deep capillary plexus significantly and progressively decreased in the no DR and mild nonproliferative DR groups compared with controls. Superficial extrafoveal avascular area, vessel density, and fractal dimension of the skeletonized deep capillary plexus had the highest diagnostic performance to differentiate mild nonproliferative DR from control eyes, with AUCs of 0.885, 0.876, and 0.876, respectively. CONCLUSION: Vessel density and fractal dimension from the skeletonized deep capillary network may be the most sensitive for detecting early retinal capillary loss in diabetes mellitus.

Author Correction: A full-width half-maximum method to assess retinal vascular structural changes in patients with ischemic heart disease and microvascular angina.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A full-width half-maximum method to assess retinal vascular structural changes in patients with ischemic heart disease and microvascular anginga.

Chest pain patients without obstructive ischemic heart disease (IHD) have increased attention in the clinical practice as carrying higher cardiovascular (CV) risk and impaired life quality. Retinal vasculature is a novel but reliable risk factor of atherosclerosis and systemic vascular diseases. However, the association of retinal blood vessels and unobstructed IHD, as known as microvascular anginga (MA) is poorly understood. This study compared retinal vascular structures of obstructive IHD and MA using spectral domain optical coherence tomography (SD-OCT) and full-width half-maximum (FWHM) methods to provide new risk predictive evidence of MA. Fundus vessels of 120 IHD patients, including 91epicardial IHD and 29 MA patients, and 66 control subjects were evaluated. Significant differences in the retinal arterial lumen diameter (RALD), retinal arterial outer diameter (RAOD), and arteriovenous ratio (AVR) have been found (P < 0.05). The severity of IHD was negatively correlated with diameters of RAOD, RALD and AVR (P < 0.05). In conclusion, there were significant differences in the retinal vascular structure between IHD patients and patients with MA. Thus, assessment of retinal vascular structure is suggested to evaluate CV risk of IHD patients, despite having no obstructive IHD.

Retinal Arteriolar Morphometry Based on Full Width at Half Maximum Analysis of Spectral-Domain Optical Coherence Tomography Images.

OBJECTIVES: In this study, we develop a microdensitometry method using full width at half maximum (FWHM) analysis of the retinal vascular structure in a spectral-domain optical coherence tomography (SD-OCT) image and present the application of this method in the morphometry of arteriolar changes during hypertension. METHODS: Two raters using manual and FWHM methods measured retinal vessel outer and lumen diameters in SD-OCT images. Inter-rater reproducibility was measured using coefficients of variation (CV), intraclass correlation coefficient and a Bland-Altman plot. OCT images from forty-three eyes of 43 hypertensive patients and 40 eyes of 40 controls were analyzed using an FWHM approach; wall thickness, wall cross-sectional area (WCSA) and wall to lumen ratio (WLR) were subsequently calculated. RESULTS: Mean difference in inter-rater agreement ranged from -2.713 to 2.658 µm when using a manual method, and ranged from -0.008 to 0.131 µm when using a FWHM approach. The inter-rater CVs were significantly less for the FWHM approach versus the manual method (P < 0.05). Compared with controls, the wall thickness, WCSA and WLR of retinal arterioles were increased in the hypertensive patients, particular in diabetic hypertensive patients. CONCLUSIONS: The microdensitometry method using a FWHM algorithm markedly improved inter-rater reproducibility of arteriolar morphometric analysis, and SD-OCT may represent a promising noninvasive method for in vivo arteriolar morphometry.

Update on retinal vessel structure measurement with spectral-domain optical coherence tomography.

This study was conducted to demonstrate a new scan method for retinal vessel structure measurement in a specific region of fundus (zone B) using spectral-domain optical coherence tomography (SD-OCT), and to assess its reliability. One temporal superior retinal vessel pair passing through a concentric ring (zone B), which was defined between half and one disc distance from the optic disc border, was chosen for the measurement using a volume scan in SD-OCT. On the SD-OCT image, retinal arteriolar outer diameter (RAOD), retinal arteriolar lumen diameter (RALD), retinal venular outer diameter (RVOD) and retinal venular lumen diameter (RVLD) were measured. Retinal vessel diameters on color fundus photographs were also analyzed. Fifty-five healthy individuals were recruited to evaluate intraobserver and interobserver reproducibility between the two examiners. The intraobserver intraclass correlation coefficient (ICC) ranged from 0.972 to 0.981, and the interobserver ICC ranged from 0.968 to 0.980. In the Bland-Altman plot, the 95% limits of interobserver agreement for the RAOD, RALD, RVOD and RVLD were -5.60 to 4.84µm, -5.78 to 5.05µm, -7.52 to 5.62µm and -7.10 to 5.63µm, respectively. The retinal arteriolar and venular lumen diameters on the SD-OCT image were close to the mean arteriolar and venular diameters obtained from the color fundus photographs. Volume scan method produced better images of retinal vessels showing the fine structures of the vessel wall, and provided reliable retinal vessel structure measurement in zone B with good repeatability and reproducibility.

[Correlation of optic retinal nerve fiber layer thickness and visual function in patients with nonproliferative diabetic retinopathy].

OBJECTIVES: To investigate the change of optic retinal nerve fiber layer (RNFL) thickness in nonproliferative diabetic retinopathy (NPDR) and to evaluate the correlation between the optic RNFL structural change and visual function. METHODS: A cross-sectional study. All cases came from ophthalmology department of Zhejiang Province Traditional Chinese Medical Hospital, and the First People's Hospital of Ningbo, and Zhongshan Ophthalmic Center, Sun Yat-Sen University from December 2009 to October 2012. All the disease and control cases were coming from the same hospitals at the same period. Subjects were divided into 3 different groups: patients with NPDR (n = 89, 89 eyes), patients with diabetic mellitus but without diabetic retinopathy (NRD) (n = 96, 96 eyes) and disease-free controls (n = 115, 115 eyes). One eye of each subject was randomly selected for study. Participants aged from 40 to 70 years at baseline and all diabetic patients had a diabetic history of at least 5 years. Optic RNFL thickness of each subject was measured by spectral domain optical coherence tomography(SD-OCT). Visual function examinations including contrast sensitivity test in spatial frequencies of 1.5, 3.0,6.0, 12.0, 18.0 cycles per degree (c/d), pattern electroretinograms (PERG) and best corrected visual acuity (BCVA) assay. The analysis of RNFL thickness in each group was performed at four preset locations of the optic disc (i.e., temporally, superiorly, nasally, and inferiorly). To assess the structure-function relationship, the BCVA,contrast sensitivity, PERG-P50 amplitude and latency to optic RNFL thickness at each quadrant were analyzed in both NPDR and NRD groups. RESULTS: The RNFL thickness at four preset locations of the optic disc (meanly, nasally, temporally, superiorly, and inferiorly) were (97.7 ± 13.0), (71.7 ± 10.3), (70.9 ± 13.3), (118.3 ± 19.7), and (123.1 ± 20.8) µm in the NPDR group; (98.6 ± 15.3), (74.8 ± 13.1), (71.8 ± 14.6), (119.5 ± 17.2), and (125.6 ± 19.9) µm in the NRD group;and (99.1 ± 11.8), (77.4 ± 12.6), (72.6 ± 13.2), (119.1 ± 18.1), and (127.1 ± 19.3) µm in the normal group. The nasally optic RNFL thickness was significantly different among the three groups (F = 8.56, P = 0.000). The thickness in the NPDR and in the NRD group were significantly thinner than that in the normal group (SNK-q test:q = 3.16, 3.11, respectively; both P < 0.05). In the NPDR group, the nasally optic RNFL thickness was significantly thinner than that in the NRD group (SNK-q test:q = 3.07, P < 0.05). The inferiorly optic RNFL thickness was also significantly different among the three groups (F = 3.841, P = 0.035). The thickness in the NPDR group was significantly thinner than that in the normal group (SNK-q test:q = 3.090, P < 0.05). Yet, the difference of inferiorly optic RNFL thickness between the NRD group and the normal or the NPDR group did not reach the level of statistical significance (SNK-q test:q = 2.101, 1.955, P > 0.05). The temporally or superiorly optic RNFL thickness,or the average thickness of optic RNFL did not differ significantly among the three groups (F = 0.985, P = 0.375; F = 0.333, P = 0.71; F = 0.975, P = 0.379, respectively). Contrast sensitivities (1.5, 3.0,6.0, 12.0, 18.0 c/d), PERG-P50 amplitude and latency were all significantly correlated with the RNFL thickness of the nasal quadrant (nasal = 0.28, 0.26, 0.3, 0.25, 0.45, 0.65, 0.48, respectively; P < 0.05) and the inferior quadrant (inferior = 0.25, 0.28, 0.27, 0.26, 0.28, 0.37, 0.71; P < 0.05) in the NPDR group. Contrast sensitivities in high spatial frequencies (6.0, 12.0, 18.0 c/d), PERG-P50 amplitude were also significantly correlated with the RNFL thickness of the nasal quadrant (nasal = 0.59, 0.45, 0.66, 0.33, respectively; P < 0.05) and the inferior quadrant (inferior = 0.46, 0.71, 0.52, 0.41, respectively; P < 0.05) in the NRD group. CONCLUSION: The optic RNFL thickness of the nasal and inferior quadrant have been already reduced in patients with NPRD and are significantly correlated with the change of vision function.

[The effect of OPTC-shRNA on the bovine retinal pigment epithelial cells and hyalocytes co-culture collagen gel contraction system].

OBJECTIVE: To investigate the OPTC-shRNA inhibiting effect on the opticin expression by the bovine hyalocytes and retina pigment epithelial (RPE) cells co-culture collagen gel contraction system. METHODS: Experimental study. The OPTC-shRNA expression vector was designed and transfected into bovine RPE cells cultured in vitro. The relative expression and the inhibition rate of the opticin protein were measured by Western blot on days 3, 5 and 7. An in vitro cells co-culture bovine type I collagen gel contraction assay was constructed consisting of the hyalocytes and RPE cells. Six groups were established in this experiments:OPTC-shRNA plasmid transfected RPE cells and hyalocytes (group A), empty plasmid transfected RPE cells and hyalocytes (group B), non-transfected RPE cells and hyalocytes (group C), non-transfected RPE cells (group D), only hyalocytes (group E), and no cells (group F). The collagen gel contractile activities of these groups were compared by One-way ANOVA, SNK-q tests and regression analysis;and the influence of the hyalocytes density variance on the collagen gel contraction in groups A, B and C were also analyzed. RESULTS: The OPTC-shRNA expression vector with significant inhibition effect was constructed and transfected into bovine RPE cells successfully. The results of Western blot analysis showed that the inhibitory rates on the opticin expression on days 3, 5 and 7 were (83.91 ± 2.88), (84.71 ± 4.27) and (82.85 ± 2.72)%, respectively. Furthermore, the differences among days 3, 5 and 7 were insignificant (F = 1.15, P > 0.05). On day 3, the gel contraction rates for the sub-groups with various hyalocytes densities (2×10(7), 1×10(8) and 5×10(8)/L) in groups A, B and C were: group A: (23.52 ± 2.08), (56.00 ± 1.02), (61.62 ± 1.73)%; group B: (16.56 ± 2.01), (36.41 ± 1.33), (49.56 ± 1.75)%; group C: (15.75 ± 1.37), (37.45 ± 1.14), (48.45 ± 1.97)%. The gel contraction rates for groups D and E were (12.18 ± 0.95)% and (10.95 ± 0.93)%, respectively; no gel contraction was observed in group F. Pairwise comparisons of the gel contraction rates were performed by SNK-q test among groups A, B and C for various hyalocyte densities. In the 2×10(7)/L cell density group, the differences between groups A and B or C were significant (q = 11.38, 2.72, respectively, P both < 0.05), the differences between B and C were insignificant (q = 1.34, P > 0.05). In the 1×10(8)/L cell density group, the differences between groups A and B or C were significant (q = 8.83, 46.22, respectively, P both < 0.05), the differences between B and C were insignificant (q = 1.34, P > 0.05). In the 5×10(8)/L cell density group, the differences between groups A and B or C were significant (q = 48.83, 46.22, respectively, P both < 0.05), the differences between groups B and C were insignificant (q = 1.74, P > 0.05). Pairwise comparisons of the sub-groups with different hyalocyte densities in groups A, B and C (comparisons of 2×10(7)/L and 1×10(8)/L, 2×10(7)/L and 5×10(8)/L, 2×10(7)/L and 2×10(7)/L, respectively), the differences were all significant (group A:q = -55.97, -65.66, -9.69, respectively; group B: q = -34.53, -57.41, -22.88, respectively; group C: q = -41.94, -63.19, -21.25, P all < 0.05). Furthermore, the regression analysis was performed between the hyalocyte density and the collage gel contraction rates in each group. The results showed that there was a positive correlation between the gel contraction rates of the co-culture collagen gel contraction system and its hyalocyte density (groups A, B, C: r = 0.919, 0.981, 0.937, respectively, P all < 0.05). Pairwise comparison of groups D and E, D and F, E and F by SNK-q test revealed q = 54.87, 49.33, 5.54, respectively, P all < 0.05. CONCLUSION: Opticin is capable of regulating the contraction of bovine hyalocytes and RPE cells co-culture collagen gel.

[Spectral domain optical coherence tomography to assess the association between the inner caliber of large retinal vessel and the primary hypertension].

OBJECTIVE: To assess the inner caliber of large retinal vessel quantitatively using spectral domain optical coherence tomography (SD-OCT) and to reveal the association between changes in the inner caliber of large retinal vessel and the primary hypertension. METHODS: A retrospective case-control study was carried out including 215 cases (with primary hypertension) and 210 controls (without primary hypertension) admitted to our hospital since 2009 and all the cases and controls were grouped according to age. SD-OCT was performed to assess the inner caliber of large retinal vessel quantitatively including retinal artery inner caliber (RAIC), retinal vein inner caliber (RVIC) and retinal arterio-venous inner caliber ratio (RAVICR). The differences in the inner caliber of large retinal vessel between the cases and the controls in each age groups were analyzed by t test. In all cases, multiple comparisons were performed according to their blood pressure level by SNK test of one way ANOVA. The RAVICR was also correlated with the following relevant determinants via multiple stepwise regression analysis: age, diastolic and systolic blood pressure. RESULTS: In each age group of cases (< 40, 40 to 49, 50 to 59, 60 to 69, ≥ 70 years), the values of RAIC were (93.0 ± 6.3), (86.2 ± 6.1), (84.5 ± 5.1), (84.0 ± 5.5), and (81.7 ± 5.4) µm respectively, and the values of RVIC were (129.4 ± 5.8), (130.7 ± 6.5), (129.6 ± 5.4), (132.2 ± 6.4), and (131.6 ± 5.1) µm respectively, and the values of RAVICR were (0.720 ± 0.07), (0.661 ± 0.06), (0.653 ± 0.04), (0.637 ± 0.06), and (0.621 ± 0.05) µm respectively. Compared with controls, RAIC (t = -4.813, -10.893, -15.689, -8.811, and -10.151 respectively; P < 0.05) and RAVICR (t = -3.276, -8.654, -13.470, -7.801, and -9.210 respectively; P < 0.05) were significantly decreased in each age group of cases. Multiple comparisons were made among each systolic and diastolic pressure groups in all cases. In systolic groups, difference of RAIC or RAVICR were significant (SNK test)between 140 to 149 mm Hg (1 mm Hg = 0.133 kPa) and 170 to 179 mm Hg group (q = 9.46, 10.61; P < 0.05), 140 to 149 mm Hg and ≥ 180 mm Hg group (q = 11.03, 13.98; P < 0.05), 150 to 159 mm Hg and 170 to 179 mm Hg group (q = 8.13, 8.82; P < 0.05), 150 to 159 mm Hg group and ≥ 180 mm Hg group (q = 9.01, 9.97; P < 0.05). In diastolic groups, difference of RAIC or RAVICR were significant (SNK test) between 90 to 99 mm Hg and 100 to 109 mm Hg group (q = 6.79, 5.95;P < 0.05), 90 to 99 mm Hg and ≥ 110 mm Hg group (q = 9.72, 10.21; P < 0.05), 100 to 109 mm Hg and ≥ 110 mm Hg group (q = 5.93, 6.07; P < 0.05). RAVICR was associated with the diastolic and systolic blood pressure revealed by the multiple stepwise regression analysis (ANOVA: F = 11.231; Standardized regression coefficient: ß = -0.024, -0.019, respectively; P < 0.05). CONCLUSIONS: Quantitative assessment for the inner caliber of large retinal vessel can be done by SD-OCT. The value of RAI and RAVICR were correlated with diastolic and systolic blood pressure in primary hypertension.

Opticin production is reduced by hypoxia and VEGF in human retinal pigment epithelium via MMP-2 activation.

Opticin, a small leucine rich repeat protein (SLRP) contributes to vitreoretinal adhesion. This study was conducted to investigate the effects of hypoxia and vascular endothelial growth factor (VEGF) on matrix metalloproteinase (MMP) mediated opticin production in retinal pigment epithelium (RPE) cells. Primary cultured human RPE cells were treated with hypoxia (low oxygen and cobalt chloride) or VEGF (0-100 ng/mL). The mRNA levels of opticin and the protein levels of intra and extracellular opticin in RPE cells were examined by RT-PCR and Western blot assay, respectively. Furthermore, the MMP activity was analyzed by zymography, and EDTA was used as an MMP inhibitor. Analysis of the effect of MMP-2 on opticin was performed by recombinant human (rh) MMP-2 stimulation in RPE cultures and by human vitreous sample digestion with activated rhMMP-2. Our results showed that opticin was expressed by primary cultured human RPE cells. Hypoxia and VEGF stimulation did not alter opticin mRNA and protein expression in RPE cells, but markedly decreased the protein levels of extracellular opticin following increased latent MMP-2 activity. The VEGF- and hypoxia induced opticin degradation in the culture medium was blocked by EDTA. Together, opticin levels in the culture medium were also reduced after rhMMP-2 treatment. In addition, opticin in human vitreous samples could be cleaved by rhMMP-2. These results reveal that VEGF and hypoxia could decrease opticin protein levels in the human RPE secretome, and that opticin may be an enzymatic substrate for MMP-2.

Transocular removal of a retrobulbar foreign body and internal patch of the posterior exit wound with autologous tenon capsule.

A case of perforating ocular injury with a retrobulbar foreign body and a large full-thickness posterior pole defect near the optic disc was scheduled for vitrectomy after primary corneal suturing. Because it was difficult to remove the retrobulbar foreign body by orbitotomy and perform the outside suture, the retrobulbar foreign body was removed through the posterior hole by a transocular approach, and an autologous Tenon capsule flap was used to internally patch the large full-thickness posterior pole defect, thus enabling silicon tamponade. After 3 months of follow-up, there was no immune response around the patch. The retina remained mostly attached with a maintained peripheral visual field, normal intraocular pressure, and good cosmetic appearance. This surgical technique may be valuable in patients with a perforating retrobulbar foreign body and a large full-thickness posterior pole defect.

[Critical role and involvement of vascular endothelial growth factor and transforming growth factor-ß2 in collagen gel contraction induced by retinal pigment epithelial cells].

OBJECTIVE: To investigate the influence of vascular endothelial growth factor(VEGF) and transforming growth factor (TGF)-ß(2) to human retinal pigment epithelium(RPE) cell differentiation, and the mechanism of collagen gel contraction mediated by RPE cells. METHODS: Experiment study. An in vitro collagen gel contraction assay was performed to evaluate the effect of cultured human RPE in addition of VEGF and TGF-ß(2) at indicated time points (24 h, 48 h and 72 h). Three groups were established in the experiment:control group, 50 µg/L VEGF group and 5 µg/L TGF-ß(2) group. The effects of both cytokines on the collagen gel contraction were analyzed by the reduced diameter of the collagen gel. And the changes of cell morphology and their transdifferentiation were assessed to estimate the possible connection between RPE transdifferentiation and collagen gel contraction. One-way ANOVA was used in conjunction with SNK-q test to assess statistical significance at different time periods within groups. RESULTS: There were differences on collagen gel contraction rates among VEGF group [(34.7 ± 3.1)%, (44.3 ± 6.0)%, (44.0 ± 7.2)%], TGF-ß(2) group [(29.3 ± 3.1)%, (31.7 ± 3.5)%, (29.0 ± 3.6)%] and control group [(20.0 ± 0.5)%, (17.3 ± 3.6)%, (19.1 ± 0.8)%] at 24 h, 48 h and 72 h after cultured (24 h: F = 26.220, P = 0.001; 48 h: F = 26.796, P = 0.001; 72 h: F = 21.522, P = 0.002), and on each time point two two comparison in the three groups (SNK-q test, P < 0.05). There were differences on protein expression level of α-smooth muscle actin (α-SMA) in 50 µg/L VEGF group and 5 µg/L TGF-ß(2) group at difference time points, respectively (TGF-ß(2) group: F = 1.134, P = 0.000; each time point: SNK-q test, P < 0.05; VEGF group: F = 279.179, P = 0.000; each time point: SNK-q test, P < 0.05). Moreover, TGF-ß(2) (5 µg/L) demonstrated stronger and more permanent gel contraction than VEGF (50 µg/L) (6 h: F = 3.646, P = 0.000; 24 h: F = 18.706, P = 0.003; 48 h: F = 124.195, P = 0.000; 72 h: F = 76.811, P = 0.000). RPE cells' form happened fibroblasts sample transformation in both VEGF group and TGF-ß(2) group. CONCLUSIONS: Both VEGF and TGF-ß(2) can induce the collagen gel contraction, partly by means of inducing the expression of α-SMA and RPE contraction, which may thus contribute to the explanations of vitro-retinal diseases.

[The effect of vascular endothelial growth factor and hypoxia on the secretion of opticin in retinal pigment epithelium cells].

OBJECTIVE: To evaluate the role of vascular endothelial growth factor or hypoxia on the secretion of opticin in retinal pigment epithelium cells. METHODS: Human RPE cells were cultured, the third to sixth passage of retinal pigment epithelium (RPE) cells were placed in 6-well culture plates at a density of 4 × 10(4)/well. For hypoxia experiment, the cells were cultured under hypoxic condition for different times. For vascular endothelial growth factor (VEGF) experiment, the media was changed to DMEM containing different concentration VEGF (1, 10, 50, 100 µg/L) for 24 h respectively. VEGF mRNA levels were determined by RT-RCR method. The protein content of opticin in RPE cells or culture media was detected by Western blot. Matrix metalloproteinase activity in culture media was analysis by zymography. One way ANOVA was used to test the comparisons between experimental groups and control group. RESULTS: Western blot experiment showed the opticin expression was not changed in RPE cells after hypoxia treatment, however was significantly decreased in culture media. Compared with control group (0.21 ± 0.03). The relative density of VEGF mRNA levels (0.81 ± 0.04, 0.67 ± 0.07) in RPE cells were increased after 12 h or 24 h hypoxia treatment (F = 483.60, P < 0.05). Opticin expression in RPE cells was also remain unchanged after vary concentration VEGF addition treatment (F = 2.16, P > 0.05), the relative density of opticin expression in VEGF conditioned culture medium were 0.65 ± 0.02, 0.52 ± 0.04, 0.23 ± 0.03, 0.30 ± 0.03 respectively, and the difference in culture media was significant compared to control group (0.73 ± 0.04) (F = 141.38, P < 0.05). Zymography indicate a matrix metalloproteinases type 2 digest band, the activities were enhanced with VEGF increasing. The decrease of opticin in culture media after VEGF treatment could be inhibited by low condition of EDTA. CONCLUSION: VEGF and hypoxia have an effect on the on the secretion of opiticin in RPE cells, it may be contributed to the increasing levels of matrix metalloproteinases type 2.