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Purpose: To investigate age-related changes in the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in the senescence-accelerated mouse (SAM)., Methods: The external and eyecup features and light and electron microscopic findings were examined in three male and two female mice of a senescence-prone mouse strain (SAM P(8)) monthly for 12 months. These results were compared with those in age-matched mice of similar background but senescence resistant (SAM R(1)). Choroidal vascular casts were prepared at 12 months in seven mice each of the SAM P(8) and SAM R(1) strains. Quantitative analysis of area of choriocapillaris was performed by automated image analysis, and the results were analyzed by paired Student's t-test., Results: We found in the SAM P(8) strain that hair loss, coarseness of hair texture, and ulceration of skin appeared and increased as the age advanced (at approximately 5-9 months). Eyecup examination showed no differences. Light and electron microscopy revealed progressively more prominent abnormalities in the RPE and Bruch's membrane mice older than 10 months. Two of the five SAM P(8) mice older than 11 months showed what appeared to be intra-Bruch's membrane choroidal neovascularization. The RPE and Bruch's membrane appeared normal in the SAM R(1) strain. In the SAM P(8), vascular casts of the choriocapillaris showed a mild but significant decrease in vascular area when compared with the SAM R(1) strain at 12 months (P = 0.011)., Conclusions: Senescence accelerated mice develop progressive age-related changes in the RPE-Bruch's-choriocapillaris complex that have features that may be relevant in the study of age-related macular changes in humans.

Background: Replacement of degenerating retinal pigment epithelial (RPE) cells has been proposed to promote photoreceptor survival in retinal pigment epithelial disease. However, allografts of RPE have a higher rate of immunological rejection. The investigators studied the effects of autotransplantation of RPE on the morphological changes in photoreceptors and choriocapillaris., Methods: RPE autotransplantation (wound type 1) was performed in 25 rabbits and compared with wounds following debridement of the RPE (wound type 2). Light and electron microscopy and scanning electron microscopy of choroidal vascular casts were performed at 3, 7, 14 and 30 days after surgery. Quantitative analysis of the choriocapillaris bed area was performed by automated image analysis and the results were analyzed by paired Student's t-test., Results: Retinal pigment epithelium was found to be monolayered and ill-differentiated at day 7. Differentiation occurred at day 30, with preservation of photoreceptors and other layers of the neurosensory retina in type 1 wounds. Type 2 wounds showed atrophy of the regenerating retinal pigment epithelium at day 14 and day 30 with loss of overlying photoreceptor cell layer. There was significant choriocapillaris regeneration in type 1 wounds compared to the type 2 wounds at day 7 (P=0.045), day 14 (P=0.028) & day 30 (P=0.06)., Conclusions: Retinal pigment epithelial autotransplantation significantly reduced photoreceptor degeneration and choriocapillaris atrophy associated with loss of retinal pigment epithelium. This procedure supports the hypothesis that RPE autotransplantation may be helpful in geographic atrophy and conditions requiring submacular surgery.

Background: Retinal pigment epithelium (RPE) and choriocapillaris play an important role in maintaining the outer retina. Clinical and experimental studies have shown that there is a close relationship between them. To examine the relationship between RPE and choriocapillaris we developed an animal model in which degeneration and regeneration of the choriocapillaris can be created easily and reproducibly., Methods: Using pigmented rabbits a retinal detachment (about 7 disk diameters) was created in the eye and the detached retina was surgically removed. A half area of the exposed RPE was mechanically debrided using a silicone brush. The other half area remained untouched. The eyes were morphologically examined at 3, 7, and 14 days and 4 and 8 weeks after the surgery using scanning or transmission electron microscopy. Changes in the choriocapillaris after the RPE debridement were also evaluated by corrosion vascular casts., Results: The debrided area was resurfaced with elongated RPE in 7 days after surgery. The replaced RPE was dedifferentiated but it gradually recovered cell polarity by 4 weeks after surgery. The choriocapillaris beneath the debrided area underwent degeneration; however, it regenerated by 4 weeks after surgery, corresponding to the timing of the morphologic recovery of the replaced RPE., Conclusion: This animal model of surgically induced degeneration and regeneration of the choriocapillaris may be useful to clarify the relationship between RPE and choriocapillaris and to study potential treatments for choroidal vascular diseases.

Purpose: To test the effects of genistein on choriocapillaris regeneration and retinal pigment epithelial (RPE) wound healing in a surgical model in the rabbit., Methods: Intravitreal injections of either 0.1 ml of a 90-microM concentration of genistein, dimethyl sulfoxide (DMSO; negative control), or 2 microg cycloheximide (positive control) were given 24 hours before surgical debridement of RPE in rabbits. Scanning electron microscopy (EM) of choroidal vascular casts and the RPE wounds and histologic evaluation by light microscopy and EM of the disturbed areas were performed at days 1, 7, and 30 after surgery. Quantitative analysis of the area of the choriocapillaris bed and RPE was performed by automated image analysis, and the results were analyzed by paired Student's t-test., Results: Loss of RPE caused a rapid initial atrophy followed by slower subsequent revascularization of the choriocapillaris, which paralleled the RPE wound healing. Choriocapillaris regeneration appeared nearly normal by day 30 in the DMSO group. Inhibition of choriocapillaris revascularization by genistein was significant at day 30 when compared with the DMSO-treated negative control (P = 0.013). There was a strong trend toward inhibition in the cycloheximide-treated positive control group (P = 0.062), which reached significance at day 7 compared with the DMSO group (P = 0.02). RPE covered the wound area by day 7 in all groups., Conclusions: Intravitreal injection of genistein was found to cause significant inhibition of choriocapillaris regeneration without apparent effect on RPE wound healing. Tyrosine kinase inhibitors such as genistein may be useful as a pharmacologic approach in the treatment of choroidal neovascularization.

The authors describe an eye with a central retinal vein occlusion that developed chorioretinal anastomoses following transvitreal venipuncture, a vitreoretinal surgical technique.

Purpose: Submacular surgery is under investigation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis syndrome, and other causes. The aims of this study were to determine whether the macular area from which choroidal neovascularization was removed surgically remained functional and whether there was any qualitative difference between eyes with different disease conditions or between eyes of younger and older patients., Methods: Our study included 19 patients (19 eyes) with choroidal neovascularization, seven cases caused by age-related macular degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia, or idiopathic causes. All tests were performed at least 6 months after surgical removal of choroidal neovascularization. All patients underwent fundus perimetry with the scanning laser ophthalmoscope for evaluation of dense and relative scotomas and fixation site., Results: After submacular surgery in 19 patients, 10 patients (one with age-related macular degeneration and nine with pathologic myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal neovascularization) fixated within an area that ophthalmoscopically and angiographically was an area of retinal pigment epithelial disturbance occupied by choroidal neovascularization preoperatively. Of 12 patients without age-related macular degeneration, seven of eight patients younger than 50 years of age compared with two of four patients 50 years or older fixated within the area of retinal pigment epithelial disturbance., Conclusions: Our data suggest that in patients without age-related macular degeneration who undergo submacular surgery, the surgically disturbed area previously occupied by choroidal neovascularization can remain functional postoperatively. Furthermore, occasionally a patient with age-related macular degeneration undergoing submacular surgery still can fixate in the area from which the choroidal neovascularization was removed.

Purpose: To report a surgical method for translocation of the foveal retina in eyes with subfoveal choroidal neovascularization., Methods: In three eyes of three patients, a crescent-shaped, partial-thickness scleral resection was performed near the equator at either the superotemporal or the inferotemporal quadrant. A near-total retinal detachment was created; then the edges of the resected sclera were sutured, causing shortening of the sclera with subsequent reattachment of the retina, resulting in translocation of the fovea to an area overlying nonfoveal retinal pigment epithelium and choroid., Results: In three eyes of three patients, the fovea was surgically translocated to overlie retinal pigment epithelium that preoperatively was not underlying the fovea. In two patients, laser photocoagulation was applied to the choroidal neovascularization that, after translocation of the fovea, was no longer subfoveal, so that the photocoagulation was not associated with immediate visual loss. After a follow-up of 4 to 6 months, the visual acuity had improved in all patients (from 20/126 preoperatively to 20/70 in one patient, from 20/200 preoperatively to 20/70 in the second, and from 20/160 to 20/30 in the third). The patients noted distortion or tilting of the images, which improved over time., Conclusions: Limited foveal translocation may offer a therapeutic modality to preserve or improve vision in cases of subfoveal choroidal neovascularization. Additional follow-up is needed to assess the impact of potential complications associated with the surgical procedure, such as retinal detachment, proliferative vitreoretinopathy, and cataract, as well as the possibility of recurrent choroidal neovascularization.

Purpose: To report a surgical method for retinal translocation as a potential treatment for eyes with subfoveal choroidal neovascularization., Methods: Thirty right eyes of 30 pigmented rabbits were used for this study. The first 15 were used to develop the technique. The complete surgical technique for retinal translocation was performed in the last consecutive 15 rabbits. Intravitreal injection of sulfur hexafluoride was performed to compress and liquefy the vitreous. Two weeks later, we used transscleral subretinal hydrodissection to create a retinal detachment. A scleral resection was then performed near the equator in the superotemporal quadrant. Fundus photographs were taken to record the retinal status before, immediately after, and 1, 3, and 7 days after surgery. Electroretinography was performed in three rabbits 3, 7, and 14 days after retinal translocation. Histologic studies were performed in one rabbit 7 days after retinal translocation., Results: Our results are based on experiments performed in the last consecutive 15 rabbits. One day after surgery, retinal reattachment was observed in 14 of the 15 animals. The remaining animal developed endophthalmitis. A predictable retinal translocation of about 1,000 microm was achieved. Retinal tears were noted on the retinal folds in four cases after 1 week. Electroretinographic studies showed transient reduction in retinal function. Mild morphologic damage to the outer retinal layers was seen histologically. Retinal detachment or proliferative vitreoretinopathy did not develop in any rabbit in the 14 days of follow-up., Conclusions: Limited retinal translocation with repositioning of the central retina was accomplished in rabbits.

Purpose: To describe the clinical outcomes of patients undergoing pars plana vitrectomy to remove subretinal neovascular membranes caused by traumatic choroidal ruptures., Methods: Three patients with traumatic choroidal rupture in whom subfoveal choroidal neovascularization developed underwent pars plana vitrectomy with surgical excision of the neovascular membrane. Surgical specimens were examined histopathologically in two patients., Results: The choroidal neovascularization was removed completely in each patient. Visual results were excellent with visual acuities improving to 20/30 or better in each patient. Recurrence of choroidal neovascularization has not been observed. Fibrovascular membranes with reactive retinal pigment epithelium were observed in two specimens examined histopathologically., Conclusion: Surgical removal of subretinal neovascular membranes emanating from traumatic choroidal ruptures produced an excellent visual outcome in three patients studied. The neovascular membranes, which were removed with minor disturbance to the underlying pigment epithelium, have similar characteristics to those obtained from patients with ocular histoplasmosis syndrome.

From a patient with age-related macular degeneration we studied ultrastructurally a disciform scar that was removed from an eye with a vitreous hemorrhage. In cross section, the scar was divided by a retinal pigment epithelial (RPE) cell layer. The choroidal side consisted of fibrovascular tissue with active neovascular buds and inflammatory cells, including macrophages attached to the RPE basement membrane. Apart from the RPE, no components of Bruch's membrane could be identified. The retinal side contained organizing hemorrhage and a collagenous matrix with fibroblastlike cells probably of RPE and choroidal origin. The anatomy and the clinical findings at surgery suggest that such scars lie on (rather than within) the inner collagenous layer of Bruch's membrane and contain two components divided by the original RPE layer. The choroidal side is fibrovascular, including active neovascularization, and the retinal side is fibrous and formed by metaplastic RPE cells and choroidal fibrovascular ingrowth.

We used vitreous surgery to treat seven patients (eight eyes) with complicated retinal detachments associated with choroidal colobomas. All eyes had large choroidal colobomas and no evidence of peripheral retinal breaks. Small, atrophic breaks were detected in five of the eyes and were located in the base of the coloboma in four of the five eyes. Adjunctive surgical techniques were necessary and included cyanoacrylate retinopexy in four eyes, silicone oil tamponade in five eyes, and retinectomy in two eyes. Retinal reattachment was ultimately attained in seven of the eight eyes. The number of surgical procedures ranged from one to five, with an average of three. Postoperative visual acuity of the eyes that underwent anatomically successful procedures ranged from 20/100 to light perception. Proliferative vitreoretinopathy was the most frequent cause of redetachment, occurring in six of the eight eyes.