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Purpose: Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable., Methods: The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable., Results: Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups., Conclusions: Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients., Translational Relevance: Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm 2 ; 4.5 J/cm 2 ) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.

Purpose: The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO)., Methods: Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO., Results: Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse., Conclusions: Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.

Purpose: To demonstrate a method for correlating photoreceptor mosaic structure with optical coherence tomography (OCT) and microperimetry findings in patients with Stargardt disease., Methods: A total of 14 patients with clinically diagnosed Stargardt disease were imaged using confocal and split-detection adaptive optics scanning light ophthalmoscopy. Cone photoreceptors were identified manually in a band along the temporal meridian. Resulting values were compared to a normative database ( n = 9) to generate cone density deviation (CDD) maps. Manual measurement of outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness was performed, in addition to determination of the presence of ellipsoid zone (EZ) and interdigitation zone (IZ) bands on OCT. These results, along with microperimetry data, were overlaid with the CDD maps., Results: Wide variation in foveal structure and CDD maps was seen within this small group. Disruption of ONL+HFL and/or IZ band was seen in all patients, with EZ band preservation in regions with low cone density in 38% of locations analyzed. Normality of retinal lamellar structure on OCT corresponded with cone density and visual function at 50/78 locations analyzed. Outer retinal tubulations containing photoreceptor-like structures were observed in 3 patients., Conclusions: The use of CDD color-coded maps enables direct comparison of cone mosaic local density with other measures of retinal structure and function. Larger normative datasets and improved tools for automation of image alignment are needed., Translational Relevance: The approach described facilitates comparison of complex multimodal data sets from patients with inherited retinal degeneration, and can be expanded to incorporate other structural imaging or functional testing.

Background: Age-related macular degeneration (AMD) is a leading cause of visual loss among the elderly. A key cell type involved in AMD, the retinal pigment epithelium, expresses a G protein-coupled receptor that, in response to its ligand, L-DOPA, up-regulates pigment epithelia-derived factor, while down-regulating vascular endothelial growth factor. In this study we investigated the potential relationship between L-DOPA and AMD., Methods: We used retrospective analysis to compare the incidence of AMD between patients taking vs not taking L-DOPA. We analyzed 2 separate cohorts of patients with extensive medical records from the Marshfield Clinic (approximately 17,000 and approximately 20,000) and the Truven MarketScan outpatient and databases (approximately 87 million) patients. We used International Classification of Diseases, 9th Revision codes to identify AMD diagnoses and L-DOPA prescriptions to determine the relative risk of developing AMD and age of onset with or without an L-DOPA prescription., Results: In the retrospective analysis of patients without an L-DOPA prescription, AMD age of onset was 71.2, 71.3, and 71.3 in 3 independent retrospective cohorts. Age-related macular degeneration occurred significantly later in patients with an L-DOPA prescription, 79.4 in all cohorts. The odds ratio of developing AMD was also significantly negatively correlated by L-DOPA (odds ratio 0.78; confidence interval, 0.76-0.80; P <.001). Similar results were observed for neovascular AMD (P <.001)., Conclusions: Exogenous L-DOPA was protective against AMD. L-DOPA is normally produced in pigmented tissues, such as the retinal pigment epithelium, as a byproduct of melanin synthesis by tyrosinase. GPR143 is the only known L-DOPA receptor; it is therefore plausible that GPR143 may be a fruitful target to combat this devastating disease., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate outer retinal structural abnormalities in patients with visual deficits after closed-globe blunt ocular trauma., Methods: Nine subjects with visual complaints after closed-globe blunt ocular trauma were examined between 1 month after trauma and 6 years after trauma. Spectral domain optical coherence tomography was used to assess the outer retinal architecture, whereas adaptive optics scanning light ophthalmoscopy was used to analyze the photoreceptor mosaic integrity., Results: Visual deficits ranged from central scotomas to decreased visual acuity. Spectral domain optical coherence tomography defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. Adaptive optics scanning light ophthalmoscopy revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss., Conclusion: We observe persistent outer retinal disruption in subjects with visual complaints after closed-globe blunt ocular trauma, albeit to a variable degree. Adaptive optics scanning light ophthalmoscopy imaging allows the assessment of photoreceptor structure at a level of detail not resolvable using spectral domain optical coherence tomography or other current clinical imaging tools. Multimodal imaging seems to be useful in revealing the cause of visual complaints in patients after closed-globe blunt ocular trauma. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various traumas.

Purpose: Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated. We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism., Methods: We recruited 32 subjects with a clinical diagnosis of albinism. DNA was obtained from 25 subjects, and known albinism genes were analyzed for mutations. Relative inner and outer segment (IS and OS) lengthening (fovea-to-perifovea ratio) was determined from manually segmented spectral domain-optical coherence tomography (SD-OCT) B-scans. Foveal pit morphology was quantified for eight subjects from macular SD-OCT volumes. Ten subjects underwent imaging with adaptive optics scanning light ophthalmoscopy (AOSLO), and cone density was measured., Results: We found mutations in 22 of 25 subjects, including five novel mutations. All subjects lacked complete excavation of inner retinal layers at the fovea, though four subjects had foveal pits with normal diameter and/or volume. Peak cone density and OS lengthening were variable and overlapped with that observed in normal controls. A fifth hyper-reflective band was observed in the outer retina on SD-OCT in the majority of the subjects with albinism., Conclusions: Foveal cone specialization and pit morphology vary greatly in albinism. Normal cone packing was observed in the absence of a foveal pit, suggesting a pit is not required for packing to occur. The degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight on this issue., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Purpose: To evaluate retinal structure and photoreceptor mosaic integrity in subjects with OPN1LW and OPN1MW mutations., Methods: Eleven subjects were recruited, eight of whom have been previously described. Cone and rod density was measured using images of the photoreceptor mosaic obtained from an adaptive optics scanning light ophthalmoscope (AOSLO). Total retinal thickness, inner retinal thickness, and outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness were measured using cross-sectional spectral-domain optical coherence tomography (SD-OCT) images. Molecular genetic analyses were performed to characterize the OPN1LW/OPN1MW gene array., Results: While disruptions in retinal lamination and cone mosaic structure were observed in all subjects, genotype-specific differences were also observed. For example, subjects with "L/M interchange" mutations resulting from intermixing of ancestral OPN1LW and OPN1MW genes had significant residual cone structure in the parafovea (∼25% of normal), despite widespread retinal disruption that included a large foveal lesion and thinning of the parafoveal inner retina. These subjects also reported a later-onset, progressive loss of visual function. In contrast, subjects with the C203R missense mutation presented with congenital blue cone monochromacy, with retinal lamination defects being restricted to the ONL+HFL and the degree of residual cone structure (8% of normal) being consistent with that expected for the S-cone submosaic., Conclusions: The photoreceptor phenotype associated with OPN1LW and OPN1MW mutations is highly variable. These findings have implications for the potential restoration of visual function in subjects with opsin mutations. Our study highlights the importance of high-resolution phenotyping to characterize cellular structure in inherited retinal disease; such information will be critical for selecting patients most likely to respond to therapeutic intervention and for establishing a baseline for evaluating treatment efficacy.

Coats disease is a well-described clinical condition featuring peripheral leakage from telangiectatic vasculature, resulting in exudative retinal detachments and exudative deposits. It often affects pediatric patients, requiring examinations and treatments to be performed under anesthesia. It can be difficult to distinguish from retinoblastoma. The RetCam II is a wide-field fundus imaging system that can also obtain intraoperative fluorescein angiography. The case of a 5-year-old girl diagnosed with Coats disease is presented. She presented with an exudative detachment, a submacular nodule, and peripheral telangiectasis. An examination under anesthesia, including angiography, was performed. The angiograph revealed characteristic aneurysms as well as extensive areas of telangiectasis and ischemia not readily visible on examination. The angiogram allowed more diagnostic certainty and guided a more complete treatment than otherwise possible. We propose that fluorescein angiography with the RetCam II system can be a useful tool when examining and treating pediatric patients with Coats disease., (Copyright 2010, SLACK Incorporated.)

Background and Objective: To quantify the interpretation of fluorescein angiograms of evolving predominantly classic choroidal neovascularization in age-related macular degeneration., Patients and Methods: Thirty-six fluorescein angiograms of predominantly classic choroidal neovascularization were used to define 22 fluorescein angiogram pairs. Imaging software was used to measure surface area and greatest linear dimension (GLD). Six retina physicians estimated the change in surface area and GLD for each pair before and after demarcation of the lesions' borders and GLD., Results: For enlarging lesions, the smallest changes consistently detected by physicians were a 5% to 15% increase in surface area and a 5% to 15% increase in GLD; for shrinking lesions, they were a 5% to 15% decrease in surface area and a 5% to 15% decrease in GLD. Linear regression demonstrated moderate correlation between physician and software estimates of surface area and GLD change (r(2) = 0.50 and 0.67, respectively; P < .001), which was higher with lesion demarcation (r(2) = 0.91 and 0.93, respectively; P < .001)., Conclusion: Computer-assisted demarcation of lesion surface area and GLD reduced variability in physicians' estimates of choroidal neovascularization size change and improved correlation with software measurements., (Copyright 2009, SLACK Incorporated.)

Scleral buckle removal is an uncommon procedure performed for various reasons. Microbiological information on explanted scleral buckles remains limited. The authors identified 37 cases of scleral buckle removal during an 18-year period. Bacterial cultures isolated an organism in 4 of 9 patients (44%) with clinical infection. Organisms identified included methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Mycobacterium abscessus, and coagulase-negative Staphylococcus species. Bacterial cultures isolated an organism in 3 of 11 patients (27%) without clinical infection. Organisms identified included Nocardia species, Alcaligenes xylosoxidans, and Mycobacterium chelonae. Scleral buckles appearing clinically infected may be associated with more virulent organisms and a greater chance of identifying an organism. Bacterial cultures may be of value for scleral buckles upon removal.

Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.

Background and Objectives: Transpupillary thermotherapy (TTT) with indocyanine green (ICG) dye enhancement (TTT+) and TTT alone were compared for safety and effectiveness as a treatment of occult subfoveal choroidal neovascularization in age-related macular degeneration., Patients and Methods: Twenty-one patients were randomized to receive TTT (12 eyes) or TTT+ (9 eyes) and observed for at least 6 months. ETDRS visual acuity and fluorescein and ICG angiography were obtained every 3 months., Results: The median initial visual acuity was 20/80 in the TTT group and 20/100 in the TTT+ group. At 6 months, loss of less than 3 lines of visual acuity was present in 7 of 12 eyes (58%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. At the final examination, there was no active choroidal neovascularization exudation in 6 of 12 eyes (50%) in the TTT group and 5 of 9 eyes (56%) in the TTT+ group. The median final visual acuity was 20/125 in the TTT group and 20/160 in the TTT+ group. Ocular or systemic complications were not encountered in either group., Conclusion: TTT with ICG dye enhancement was as safe and effective as TTT alone in this study. However, modifications of treatment protocol would be needed to see whether there is any advantage to using ICG dye enhancement.

Purpose: To evaluate the efficacy of transpupillary thermotherapy (TTT) in management of occult subfoveal choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD)., Methods: Retrospective chart review of eyes that were treated with TTT and had at least 12 weeks of follow-up. Base-line and final ETDRS visual acuity and fluorescein angiography (FA) were compared., Results: For the 48 eyes which met inclusion criteria, mean pre-operative visual acuity was 20/128 (range: 20/50-20/500). Average follow-up was 27 weeks (range: 12 weeks-55 weeks). At 3 months after treatment, 12 eyes (25%) improved 2 lines or more, 18 eyes (37.5%) had no change or 1 line of visual improvement, and 18 eyes (37.5%) worsened 1 or more lines. No significant adverse event was noted during treatment. Three eyes developed large submacular hemorrhage within 2 months of treatment. Based on clinical examination and FA, 61% of the eyes appeared to have reduction of subretinal fluid compared to pre-operative evaluations., Conclusion: Visual acuity was stable or improved in 62.5% of eyes in our series and the treatment was well tolerated. Longer follow up and larger number of patients would be required to evaluate the ultimate benefit of TTT in management of occult CNV due to AMD.

Objective: To determine the effect of endophthalmitis on diabetic retinopathy., Design: Noncomparative case series., Methods: The records of all consecutive patients with endophthalmitis treated between 1992 and 1997 at the Medical College of Wisconsin were retrospectively reviewed. Those patients with diabetes mellitus were analyzed., Participants: From 77 reviewed records, 11 patients (12 eyes; 14%) were identified as diabetics with endophthalmitis and were studied., Main Outcome Measures: Stage of diabetic retinopathy, time to retinopathy progression, and visual acuity., Results: Mean patient age was 68 years, and mean duration of diabetes was 11.7 years. Mean patient follow-up was 17 months. Of the six cases without evidence of retinopathy before the endophthalmitis, none went on to develop retinopathy. Of six eyes with pre-existing nonproliferative retinopathy, four showed evidence of progression within 6 months of the infection. Three developed severe proliferative disease and macular edema, and one developed severe nonproliferative disease. More patients without pre-existing retinopathy achieved a final visual acuity of 20/40 or greater., Conclusions: Patients with pre-existing diabetic retinopathy may be at increased risk for rapid retinopathy progression and a poorer visual outcome after endophthalmitis. These results support the concept that inflammation may exacerbate diabetic retinopathy.

Objective: To report the visual and anatomic outcome after surgical drainage of suprachoroidal hemorrhage according to hemorrhage severity., Design: A retrospective chart review., Participants: Forty-eight consecutive eyes undergoing surgical drainage of a suprachoroidal hemorrhage at The Medical College of Wisconsin were examined., Intervention: Demographic and clinical data were abstracted from patients' medical records. Eyes were classified into four categories of increasing hemorrhage complexity: (1) nonappositional choroidal hemorrhage without vitreous or retinal incarceration in the wound (12 eyes); (2) centrally appositional choroidal hemorrhage without vitreous or retinal incarceration in the wound (17 eyes); (3) choroidal hemorrhage with associated vitreous incarceration in the wound (11 eyes); and (4) choroidal hemorrhage with associated retinal incarceration in the wound (8 eyes)., Main Outcome Measures: Visual acuity, rate of persistent hypotony, and incidence of irreparable retinal detachment after surgical drainage for four classes of suprachoroidal hemorrhage were defined., Results: Overall, 11 (23%) of 48 eyes had no light perception (NLP) vision develop, 9 (19%) of 48 eyes had persistent postsurgical hypotony (intraocular pressure < 6), and 21 (64%) of 33 eyes with retinal detachment enjoyed successful retinal reattachment surgery. A definite trend toward an increased rate of NLP vision (P < 0.02), persistent hypotony (P < 0.05), and irreparable retinal detachment (P = 0.11) was observed with increasing suprachoroidal hemorrhage complexity. Eyes with retinal incarceration, compared to eyes without retinal incarceration, had an increased rate of NLP vision (63% vs. 15%; P < 0.01), persistent postsurgical hypotony (50% vs. 13%; P < 0.05), and irreparable retinal detachment (50% vs. 20%; P = 0.07)., Conclusions: Eyes requiring surgical drainage of a suprachoroidal hemorrhage have a guarded prognosis, with a poorer outcome associated with increasing hemorrhage complexity. A classification system incorporating choroidal apposition, and vitreous and retinal incarceration in the wound, provides a format for reporting and assessing the efficacy of management strategies in this condition.

Objectives: To assess retinal complications and to identify risk factors for retinal complications following aqueous shunt procedures., Materials and Methods: Records of 38 consecutive aqueous shunt procedures that were performed on 36 patients at the Eye Institute of the Medical College of Wisconsin, Milwaukee, from June 1993 to March 1995 (minimum follow-up, 6 months) were reviewed. The mean +/- SD follow-up was 11.4 +/- 5.2 months (median, 10.5 months)., Results: Twelve patients (32%) had the following retinal complications: 4 serous choroidal effusions (10%) that required drainage, 3 suprachoroidal hemorrhages (8%), 2 vitreous hemorrhages (5%), 1 rhegmatogenous retinal detachment (3%), 1 endophthalmitis (3%), and 1 scleral buckling extrusion (3%). Surgical procedures for retinal complications were required in 8 (67%) of these 12 patients. Visual acuity decreased 2 lines or more in 9 (75%) of these 12 patients. The median onset of a postoperative retinal complication was 12.5 days, with 10 patients (83%) experiencing complications within 35 days. Serous choroidal effusions developed in 10 other patients (26%), and these effusions resolved spontaneously. Visual acuity decreased 2 lines or more in 2 (20%) of these additional 10 patients. Patients who experienced serious retinal complications were significantly older, had a higher rate of hypertension, and postoperative ocular hypotony. Serious retinal complications were distributed evenly among patients with Krupin valves with discs and Molteno and Baerveldt devices. Experience with the Ahmed glaucoma valve implant was limited., Conclusion: Aqueous shunt procedures may be associated with significant retinal complications and subsequent visual loss.

Background: Visual recovery after submacular surgery for age-related macular degeneration (AMD) has been very limited., Methods: A patient with an extrafoveal fibrotic choroidal neovascular membrane from AMD had an overlying serous foveal detachment with the fibrotic tissue elevating the foveal retina. Photocoagulation of the neovascular membrane was not recommended because of its nonpigmented, fibrotic nature. The membrane was surgically excised., Results: Preoperative and postoperative visual acuity and central 30 degrees visual fields were followed. Visual acuity improved from 20/200 to 20/25, and a preoperative central scotoma resolved completely 18 months after surgical excision of the extrafoveal fibrotic neovascular membrane. There were no intraoperative or postoperative complications., Conclusion: This type of patient may represent a distinct subset of patients with AMD amenable to subretinal surgery who could potentially have good recovery of vision.

Amiloride is an inhibitor of urokinase-type plasminogen activator, and might therefore have an inhibitory effect on neovascularization. Neovascularization was induced in rabbit corneas via local implantation of prostaglandin E1 pellets prepared in a slow-release polymer. Animals received daily intraperitoneal injections of 30 mg of amiloride, or an equivalent volume of saline solution for 5 days; both were well tolerated without severe untoward effect. Neovascular response, as documented by corneal photographs, was evaluated after 5 days of injections. The area of induced corneal neovascularization was decreased by 55% in animals receiving amiloride when compared with controls. Thus, amiloride and similar compounds may prove useful in the study and management of neovascularization.

A retina-derived substance (or substances) has been identified that stimulates vascular endothelial cells to degrade three structural components of basement membrane: type IV collagen, fibronectin and laminin. In basement membrane surrounding existing blood vessels, endothelial cells stimulated in this way can presumably migrate through the resulting gaps and form new vascular sprouts. These events may therefore represent the earliest steps in the formation of new blood vessels.

Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.

Transforming growth factor beta (TGF-beta) stimulates fibrosis. We studied its possible role as a bioactive substance for inducing localized chorioretinal wound healing along the edge of a retinal tear. The TGF-beta was applied to induced retinal tears that were examined histopathologically. One day after surgery, neither control nor TGF-beta-treated eyes developed chorioretinal wound healing. Four days, two weeks, and two months after surgery, the control eyes still had not developed chorioretinal wound healing. In contrast, the edges of the retinal tear treated with TGF-beta were adherent to the underlying Bruch's membrane via localized fibrous tissue without apparent effects elsewhere. These results demonstrate intraocular in vivo bioactivity of TGF-beta and suggest that TGF-beta may have a potential role as an alternative means for inducing a chorioretinal adhesion in the treatment of retinal tears.