Recognition of Glaucomatous Fundus Images Using Machine Learning Methods Based on Optic Nerve Head Topographic Features.

PURPOSE: The aim was to compare the effectiveness of clinical discriminant rules and machine learning classifiers in identifying glaucomatous fundus images based on optic disc topographic features. DESIGN: Retrospective case-control study. METHODS: The study used a total of 800 fundus images, half of which were glaucomatous cases and the other half non- glaucomatous cases obtained from an open database and clinical work. The images were randomly divided into training and testing sets with equal numbers of glaucomatous and non-glaucomatous images. An ophthalmologist framed the edge of the optic cup and disc, and the program calculated five features, including the vertical cup-to-disc ratio and the width of the optic rim in four quadrants in pixels, used to create machine learning classifiers. The discriminative ability of these classifiers was compared with clinical discriminant rules. RESULTS: The machine learning classifiers outperformed clinical discriminant rules, with the extreme gradient boosting method showing the best performance in identifying glaucomatous fundus images. Decision tree analysis revealed that the cup-to-disc ratio was the most important feature for identifying glaucoma fundus images. At the same time, the temporal width of the optic rim was the least important feature. CONCLUSIONS: Machine learning classifiers are an effective approach to detecting glaucomatous fundus images based on optic disc topographic features and integration with an automated program for framing and calculating the required parameters would make it a straightforward and effective approach.

Long-Term Follow-Up of Refractory Large Macular Hole with Autologous Neurosensory Retinal Free Flap Transplantation.

Purpose: To evaluate the long-term anatomic and functional outcomes of autologous neurosensory retinal free flap transplantation (ART) for patients with refractory large macular hole (MH). Design: Retrospective interventional case series. Methods: We reviewed 9 patients who underwent ART for their refractory large MH. In this extended follow-up study, postoperative assessment including spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) were recorded at 12, 15, 18, 21, and 24 months after surgery. Results: The macular hole of all patients appeared successfully closed during the whole follow-up period. The mean logMAR BCVA improved from 1.61 ± 0.44 (preoperative) to 0.72 ± 0.30 (12 months after surgery) (p < 0.001). Thereafter, the mean BCVA remained stable at each follow-up. At the mean 16.0 ± 0.8 months postoperatively, inner retinal cystic changes were observed in 4 eyes (44.4%), but these did not significantly affect vision. Conclusion: ART is a good alternative technique for closing large refractory macular holes. Although inner retinal cystic changes were observed in 4 eyes (44.4%), this phenomenon did not significantly affect visual acuity. It provides long-term good anatomical and functional results, especially in cases where insufficient ILM or lens capsule are left.

A refractory malignant glaucoma posttrabeculectomy in vitrectomized eye: A case report and review of the literature.

The objective of this study is to report a case of refractory malignant glaucoma post trabeculectomy in vitrectomized eye and review of previous literature in PubMed database. A 63-year-old male encountered malignant glaucoma after trabeculectomy in vitrectomized eye. We had tried vitreous tapping with peripheral iridectomy and vitreous tapping with intracameral injection of room air (Chandler procedure). All of previous procedures were in vain. Finally, the yttrium-aluminum-garnet laser membranectomy with zonulectomy was done. The intraocular pressure is within normal range without any topical glaucoma eye drops during 3-year outpatient department regular follow-up. Complete vitrectomy with a patent tunnel from posterior chamber to anterior chamber (iridectomy-zonulectomy) is the effective procedure to manage of malignant-like glaucoma.

MANAGEMENT OF REFRACTORY LARGE MACULAR HOLE WITH AUTOLOGOUS NEUROSENSORY RETINAL FREE FLAP TRANSPLANTATION.

PURPOSE: To investigate the morphological and functional outcome of refractory large macular hole (MH) with autologous neurosensory retinal free flap transplantation. METHODS: This case series enrolled 10 patients suffering from refractory large MH at Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. All eyes underwent pars plana vitrectomy, a neurosensory retinal free flap with a 1.5 to 2-MH diameter was harvested. We used an adhesive agent such as whole blood or Viscoat to assist the stabilization of the retinal free flap and then use tamponade silicone oil to tamponade the vitreous cavity. Silicone oil was removed 6 months postoperatively. Main outcome measures including closure of MH and change in best-corrected visual acuity change were recorded. RESULTS: The mean age was 64.9 ± 11.5 years. Before presentation, all cases had received at least two vitreoretinal procedures including vitrectomy, internal limiting membrane peeling, and fluid-gas exchange. At last visit, closure of the MH was achieved in 9 of 10 (90%) cases. The mean preoperative best-corrected visual acuity and that after 12 months of surgery improved from 1.65 ± 0.43 logarithm of minimum angle of resolution to 0.88 ± 0.49 logarithm of minimum angle of resolution (P < 0.001). CONCLUSION: For eyes with refractory or large MH, autologous neurosensory retinal free flap under silicone oil tamponade may provide a new option to improve the anatomical and function outcome, especially in cases where insufficient internal limiting membrane is left.

THE ASSOCIATION BETWEEN CENTRAL SEROUS CHORIORETINOPATHY AND SLEEP APNEA: A Nationwide Population-Based Study.

PURPOSE: To identify the association between sleep apnea (SA) and central serous chorioretinopathy (CSC). METHODS: In this nationwide population-based study using the Taiwan National Health Insurance Database, we enrolled adult patients with a diagnosis of SA and matched each patient to 30 age- and gender-matched control subjects without any SA diagnosis. Using Poisson regression analyses, the incidence rate of CSC was compared between SA patients and control subjects. RESULTS: A total of 10,753 SA patients and 322,590 control subjects were identified. After adjusting for age, gender, residency, income level, and comorbidities, the incidence rate of CSC was significantly higher in SA patients than in the control subjects (adjusted incident rate ratio for probable SA: 1.2 [95% CI: 1.1-1.4], P < 0.0001). Analyses of the propensity score-matched subpopulations also confirmed our findings. Risk factors for CSC in SA patients included male gender, age ≤50 years, higher income, presence of heart disease, absence of chronic pulmonary disease, and presence of liver disease. In SA patients, those who had received continuous positive airway pressure titration had a significantly lower incidence rate of CSC than the others. CONCLUSION: Our study revealed a significantly higher incidence rate of CSC in SA patients compared with the control subjects.

Comparison of Visual Outcome and Morphologic Change between Different Surgical Techniques in Idiopathic Epiretinal Membrane Surgery.

PURPOSE: To investigate the morphological and functional outcomes of idiopathic epiretinal membrane (ERM) surgery between three different surgical techniques: ERM peeling only, whole-piece ILM peeling, and maculorrhexis ILM peeling. PATIENTS AND METHODS: This is a retrospective, consecutive, and comparative study enrolling 60 patients from Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Surgery performed between July 2011 and June 2012 was done with ERM peeling only (group I). ERM peeling and ILM peeling as a whole piece (group II) were performed between July 2012 and July 2013. Surgery performed between August 2013 and December 2014 was done with maculorrhexis ILM peeling (group III). Main outcome measures include visual acuity change (BCVA) and central foveal thickness (CFT). RESULTS: At 12 months postoperation, the mean BCVA in group III was significantly better than in group I and group II. Comparison of CFT reduction between the three groups revealed significantly more reduction in group III than in group II at all postoperative follow-up periods. Eyes with restoration of foveal depression were observed in 52.6% in group I, 52.4% in group III, but only 20% of eyes in group II. None of the eyes in both ILM peeling groups encountered recurrence of macular pucker formation. CONCLUSION: All three techniques can achieve visual acuity improvement and macular thickness reduction. Maculorrhexis ILM peeling achieves more rapid improvement of visual function, better final visual outcome, and a higher rate of normal foveal contour than whole-piece ILM peeling.

Dexamethasone Intravitreal Implant (Ozurdex) for Long-Term Macular Edema after Epiretinal Membrane Peeling Surgery.

PURPOSE: To investigate the functional and anatomical outcome of the 0.7 mg dexamethasone (Ozurdex) intravitreal implant (IVD) in eyes with long-term macular edema after macular epiretinal membrane removal. METHODS: We enrolled 40 eyes with persistent macular edema at least 12 months after epiretinal membrane removal. Twenty eyes in the IVD group received IVD and the other 20 eyes were in the control group. The main outcome measures were change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT). RESULTS: For eyes in the IVD group, the mean BCVA improved by 3.45 lines to 0.47 logMAR one month after IVD. However, the mean BCVA improved by only 0.14 lines to 0.74 logMAR at the same time in eyes in the control group. Six months later, the mean BCVA improved to 0.31 and 0.74 logMAR in the IVD and control groups, respectively. In the IVD group, the mean CFT decreased rapidly by 116.8 µm to 333.9 µm one month after IVD. Thereafter the CFT decreased at a slower pace. In the control group, the CFT remained static during the follow-up period. However, in the IVD group, 6 months after IVD, the CFT seemed to have a tendency to increase. CONCLUSIONS: Single IVD could significantly decrease macular edema and improve visual outcome for eyes with persistent long-term macular edema after macular ERM removal and the effect can be sustained as long as 6 months after the initial injection. However, in order to maintain the visual and anatomical outcome, repeat IVD might be considered if macular edema recurs.

Ocular genetics in Taiwan.

PURPOSE OF REVIEW: Ocular genetics is an emerging specialty which has accompanied the advancement of modern genetic technology. This review is to understand the current status of practice in ocular genetics in Taiwan. RECENT FINDINGS: There is only one ocular genetics clinic in Taiwan. Certified clinical laboratories provide few gene tests in ocular genetics. Most ocular genetic study is focused on myopia. Financial obstacles are a major problem for patients to seek gene tests. SUMMARY: Despite a relatively successful, healthcare system in Taiwan, when compared with developed countries, ocular genetics is at an early stage of development. More financial resources and labor are needed to advance clinical care and research.

Modified internal limiting membrane peeling technique (maculorrhexis) for myopic foveoschisis surgery.

PURPOSE: Myopic foveoschisis occurs in 9-34% of highly myopic eyes with posterior staphyloma. The pathogenesis is still not fully understood. But the relative inflexibility of the inner retina and a tangential traction induced inward traction force in the posterior staphyloma are possible mechanisms. Conventional internal limiting membrane (ILM) peeling generally yields good results. However, a postoperative full-thickness macular hole happens in 13-28% of cases. Therefore, this study describes a modified ILM peeling technique named 'ILM maculorrhexis' to minimize the occurrence of postoperative macular hole in patients with foveoschisis. METHODS: This retrospective case review that included 10 eyes of 10 consecutive patients who underwent vitrectomy with ILM maculorrhexis to treat myopic foveoschisis was studied. After surgery, complete ophthalmic examination and SD-optic coherence tomographic examinations were performed 1, 3, 6, 9 and 12 months postoperatively. RESULTS: After surgical intervention, the foveoschisis resolved dramatically in all 10 eyes. The mean central foveal thickness decreased significantly from 840 µ to 273 µ at 12 months postoperatively. Mean LogMAR best-corrected visual acuity improved from 1.04 preoperatively to 0.59 12 months postoperatively. After the follow-up time of at least 12 months, all 10 eyes remained fovea attached, and none of the 10 eyes developed macular hole. CONCLUSIONS: This technique minimizes traction force over the extremely thinned foveal tissue in highly myopic eyes. In the long-term follow-up of at least 12 months, all 10 cases had good anatomic and visual results. But we still need a larger case number and longer follow-up for further evaluation.

Glaucomatocyclitic Crises May Occur in Patients with Narrow or Closed Angles.

PURPOSE: To report cases of glaucomatocyclitic crises and discuss the possibility of occurrence in patients with narrow or closed angles. BACKGROUND: The prevalence of angle closure is much higher among Asians than among the Western population. Currently, there is no evidence for a direct relationship between the etiology and angle structure. DESIGN: A retrospective and observational case series. METHODS: We retrospectively collected data from nine adult patients (three males and six females) who were diagnosed with a glaucomatocyclitic crisis and a shallow anterior chamber over a 21-year period, from 1995 to 2016, at the Kaohsiung Medical University Hospital. A narrow angle was defined as a grade less than the Shaffer system grade II. Ophthalmic examinations, including anterior segment biomicroscopy, direct ophthalmoscopy, intraocular pressure measurements, anterior chamber reaction, visual field tests, and the grade of the anterior chamber angle according to the Shaffer system, were reviewed. RESULTS: These patients experienced at least one typical unilateral ocular hypertensive episode that fulfilled the criteria of a glaucomatocyclitic crisis without the angle feature. All patients had gonioscopically narrow or closed angles with or without peripheral anterior synechiae. CONCLUSIONS: The coexistence of narrow or closed angles and a glaucomatocyclitic crisis is possible, especially in patients of Asian descent. In patients with shallow anterior chambers, a glaucomatocyclitic crisis may be a cause of acute glaucoma episodes.

Hypoxia-induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia-inducible factors-1α protein.

BACKGROUND: Hypoxia is the most important stimulus leading to up-regulation of vascular endothelial growth factor (VEGF) in the retina via elevation of hypoxia-inducible factors-1α (HIF-1α) protein. The purpose of this study was to test the effects of melatonin on the expression of VEGF and HIF-1α in the cultured human retinal pigment epithelial (RPE) cells under normoxia and hypoxia. METHOD: An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2 ) to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without melatonin under normoxia and hypoxia. The protein and RNA levels of VEGF and HIF-1α were measured by ELISA kits and RT-PCR, respectively. RESULT: Hypoxia induced a significant increase of expression and secretion of VEGF and accumulation of HIF-1α protein in RPE cells (P < 0.05). Melatonin at 10-5 to 10-8 M significantly inhibited hypoxia-induced expression, the secretion of VEGF and the accumulation of HIF-1α protein (P < 0.05), but not affected expression of VEGF and HIF-1α under normoxia (P > 0.05). CONCLUSION: This study suggests that melatonin may have potential value in the prevention and treatment of various retinal diseases associated with increase of VEGF, vascular leakage and angiogenesis.

Tolerability and efficacy of bimatoprost 0.01 % in patients with open-angle glaucoma or ocular hypertension evaluated in the Taiwanese clinical setting: the Asia Pacific Patterns from Early Access of Lumigan 0.01 % (APPEAL Taiwan) study.

BACKGROUND: In randomized, controlled trials of open-angle glaucoma (OAG) or ocular hypertension (OHT), bimatoprost 0.01 % improved tolerability while retaining the intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.03 %. Given geographic/racial differences in glaucoma presentation, the APPEAL study assessed the occurrence and severity of hyperemia produced by bimatoprost 0.01 %, and its efficacy, in the Taiwanese clinical setting. METHODS: In this multicenter, open-label, observational study, treatment-naïve and previously treated patients with OHT or OAG received once-daily bimatoprost 0.01 % for 12 weeks. Hyperemia (primary endpoint) was graded at baseline, week 6, and week 12 using a photonumeric scale (0, +0.5, +1, +2, +3), grouped (≤ +1, none to mild; ≥ +2, moderate to severe), and reported as unchanged from baseline, improved, or worsened. IOP assessments followed the same schedule. Supplemental efficacy analyses were conducted based on previous therapies. RESULTS: The intent-to-treat population (N = 312) included treatment-naïve (13.5 %) and previously treated (86.5 %) patients; mean age was 53.3 years. At baseline, 46.3 % of previously treated patients were receiving prostaglandin analog (PGA) monotherapy. At week 12, 91.2 %, 5.9 %, and 2.9 % of treatment-naïve patients exhibited unchanged, worsened, and improved hyperemia from baseline, respectively; 77.9 %, 12.9 %, and 9.2 % of previously treated patients showed no change, worsening, and improvement, respectively. There were no statistically significant shifts in hyperemia severity in either group, or in subgroups based on previous use of any PGA, any non-PGA, latanoprost, or travoprost monotherapies. In treatment-naïve patients, mean IOP reduction from baseline (18.0 ± 3.8 mm Hg) was 3.6 mm Hg at week 12 (P < 0.0001); 83.3 % had baseline IOP ≤ 21 mm Hg. In previously treated patients, mean additional IOP reduction from baseline (17.8 ± 3.9 mm Hg) was 2.6 mm Hg (P < 0.0001); similar results were observed in patient subgroups based on previous therapies. CONCLUSIONS: In the Taiwanese clinical setting, bimatoprost 0.01 % provided significant IOP lowering in treatment-naïve patients (regardless of baseline IOP) and previously treated patients (even those with relatively low IOP on other therapies), while causing no significant changes in hyperemia from baseline. TRIAL REGISTRATION: Clinicaltrials.gov NCT01814761 . Registered 18 March 2013.

5-Fluorouracil-Induced Apoptosis Changes in Cultured Corneal Epithelial Cells.

PURPOSE: Repeated subconjunctival injections with 5-fluorouracil (5-FU) after trabeculectomy are used in glaucoma patients for the inhibition of overproliferation in wound site. Thus, a certain amount of the drug may penetrate into epithelial layer, where it causes toxicity to corneal epithelial cells. The aim of this study was to evaluate the toxic effects of 5-FU and mechanisms of drug-induced apoptosis in cultured corneal epithelial cells. METHODS: Cellular damage and the caspase pathway were estimated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic characteristics were detected by flow cytometry, a TUNEL test, and western blotting in cultured corneal epithelial cells. RESULTS: The results indicated that 5-FU was toxic to corneal epithelial cells in a time- and dose-dependent manner. Pretreatment with a general caspase inhibitor (Z-VAD-FMK), a caspase-8 inhibitor (Z-IETD-FMK), and a caspase-9 inhibitor (Z-LEHD-FMK) reversed 5-FU-induced cellular damage. Following exposure to 5-FU, a flow cytometric assay with MitoLight dye demonstrated the significant loss of mitochondrial membrane potential. A positive TUNEL test revealed that cellular DNA apoptosis occurred following exposure to 0.5, 1, and 5 mg/mL 5-FU for 15 h. Positive annexin V-FITC and negative propidium iodide (PI) staining indicated that the cell membrane exhibited apoptosis upon exposure to 1 and 5 mg/mL 5-FU for 15 h. The western blot assay demonstrated upregulation of the p21 protein but downregulation of the Bcl-2 proteins induced by 5-FU. CONCLUSION: These data reveal that 5-FU-induced cellular apoptosis in corneal epithelial cells may be mediated through caspase-8, caspase-9, and mitochondria-regulated pathways, as well as by upregulation of p21 and downregulation of Bcl-2-dependent signal transduction pathways.

Correlation Between the Dynamic Postoperative Visual Outcome and the Restoration of Foveal Microstructures After Macular Hole Surgery.

PURPOSE: To analyze the long-term dynamic healing process of outer retinal changes for 1 year in patients who underwent a standard vitrectomy procedure for idiopathic macular hole (MH) repair. DESIGN: Retrospective, consecutive, observational case series. METHODS: Data were collected on 60 eyes of 56 patients (30 women, 26 men) that underwent successful pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peeling for idiopathic MH from January 2011 to December 2012. The age distribution ranged from 56 to 85 years (mean: 64 years). Forty eyes underwent combined phacoemulsification, PPV, ILM peeling, and intraocular lens implantation; 20 preoperative pseudophakic eyes underwent PPV and ILM peeling only. The main outcome measures included logMAR best-corrected visual acuity (BCVA) and macular microstructures determined by spectral-domain optical coherence tomography performed pre- and postoperatively during follow-up visits at 1, 3, 6, 9, and 12 months. RESULTS: One month after surgery, 24 eyes (40%) showed normal external limiting membrane (ELM), 36 eyes (60%) showed normal ELM at 3 months, and 54 eyes (90%) showed normal ELM 12 months after surgery. Six eyes (10%) revealed a continuous ellipsoid zone (EZ) at 1 month, 18 eyes (30%) at 3 months, and 48 eyes (80%) at 12 months postoperatively. There were no eyes with a disrupted ELM in the presence of an intact EZ line. The eyes with intact ELM and/or intact EZ line showed better BCVA than eyes with defects in ELM or EZ line. On the contrary, glial cell presentation is significantly associated with worse postoperative BCVA. However, the presence of foveal cystoid change is not significantly associated with postoperative BCVA. CONCLUSIONS: The ELM and EZ line at the fovea recovered and the presence of glial cells and cystoid space resolved gradually after surgery. The postoperative visual acuity was correlated with resolved glial cells and a restored ELM and EZ line.

Management of hypotony after glaucoma filtering surgery.

A 39-year-old male with open angle glaucoma in both eyes visited our clinic. The intraocular pressure (IOP) of both eyes fluctuated between 15 mmHg and 25 mmHg. The best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in the left eye. He underwent trabeculectomy with an adjunctive agent (mitomycin C; concentration, 0.2 mg/mL) smoothly on the right eye. After the removal of releasable sutures, the filtering bleb was prominent over the superior limbus for 3 consecutive clock hours with an IOP of about 4-5 mmHg. The Seidel test result was negative, and the anterior chamber depth was moderate to deep. The BCVA of the right eye decreased to 20/100, and optical coherence tomography revealed macular edema. We injected sodium hyaluronate (Healon, Abbott Medical Optics, Santa Ana, CA, USA) into the anterior chamber 2 months after the operation, and repeated the same procedure 4 days later. After each injection, the IOP spiked up to 50 mmHg, and an intravenous infusion of mannitol was required. Sodium hyaluronate was found migrating into the bleb on post-injection day 1. Then we decided to revise the bleb by suturing the scleral flap at two sides. The IOP of the right eye returned to 10 mmHg 4 days after the revision surgery. The BCVA of the right eye recovered to 20/20 6 months after the revision. Optical coherence tomography also showed recovery from macular edema. One IOP-lowering agent (1% brinzolamide ophthalmic suspension) was required for IOP control after bleb revision. Early revision of the scleral flap may resolve hypotony and associated serious complications.

The oculocardiac reflex during strabismus surgery: its relationship to preoperative clinical eye findings and subsequent postoperative emesis.

PURPOSE: To compare the occurrence of significant bradycardia due to the oculocardiac reflex (OCR) during strabismus surgery and its relationship to preoperative clinical eye findings and subsequent development of postoperative emesis. METHODS: The medical records of consecutive patients who underwent strabismus surgery August 2006 to June 2009 were retrospectively reviewed. OCR was defined as presence of dysrhythmia or a sudden heart rate decrease ≥ 20% after traction on the extraocular muscle. OCR incidence was compared between the first, second, and third (if any) extraocular muscles in patients who had multiple-muscle strabismus surgery and also between specific muscles (eg, medial rectus vs lateral rectus muscle). Associations with OCR were compared for different strabismus types. Vomiting was considered postoperative if it occurred before discharge of the patient at noon on the day following surgery. Risk factors for OCR and postoperative vomiting were evaluated by logistic regression analysis. RESULTS: A total of 111 records were reviewed; 41 patients (37%) experienced OCR. Incidence of OCR and absence of OCR during traction of the first muscle were significantly associated with events during traction of the second (χ(2) = 36.681, P < 0.001) and third muscles (Fisher exact test, P = 0.030). The best predictors of OCR were the absence of fine stereopsis and a larger number of surgically treated muscles. Of the 111 patients, 30 (27%) who had postoperative vomiting, the best predictors were female sex and young age. CONCLUSIONS: In our cohort, patients experiencing intraoperative OCR when the first extraocular muscle was manipulated during multiple-muscle strabismus surgery were likely to experience it again during traction of additional muscles. More severe postoperative vomiting was common in these patients. OCR was associated with the preoperative absence of fine stereopsis.

Pharmacological implications from the adhesion-induced signaling profiles in cultured human retinal pigment epithelial cells.

Extracellular matrix (ECM) plays an active and complex role in regulating cellular behaviors, including proliferation and adhesion. This study aimed at delineating the adhesion-induced signaling profiles in cultured human retinal pigment epithelium (RPE) cells and investigating the antiadhesion effect of antiproliferative drugs in this context. RPE R-50 cells grown on various ECM molecules, such as type I and IV collagens, fibronectin, and laminin, were used for adhesion assay and for examining the phosphorylation profiles of signaling mediators including Akt, extracellular signal-regulated kinase (ERK) 1/2, and integrin-linked kinase (ILK) using Western blotting. The cells receiving antiproliferative drug treatment at subtoxic doses were used to evaluate their antiadhesive and suppressive effects on kinase activities. ECM coating enhanced adhesion and spreading of RPE cells significantly. The cellular attachment onto ECM-coated surfaces differentially induced Akt, ERK1/2, and ILK phosphorylation, and concomitantly increased p53 phosphorylation and cyclin D1 expression, but decreased Bcl-2/Bax ratios. Treatment with antiproliferative agents, including 5-fluorouracil, mitomycin C, and daunomycin, at subtoxic doses suppressed the ability of RPE cells to adhere to ECM substratum significantly. This suppression was in part mediated through reduction of integrin ß1 and ß3 expressions and interfering Akt-ILK signaling activity. Mechanistically, blockade of PI3K/Akt signaling resulted in the suppressed adhesion of RPE cells to ECM. These findings support the hypothesis that, in addition to their antimitogenic effect, antiproliferative agents also exhibit suppressive effect on the adhesiveness of cultured RPE cells. Moreover, inhibitors of the PI3K/Akt signaling mediator can potentially be used as therapeutic agents for proliferative vitreoretinopathy.