Repair of the degenerate retina by photoreceptor transplantation.

Despite different aetiologies, age-related macular degeneration and most inherited retinal disorders culminate in the same final common pathway, the loss of photoreceptors. There are few treatments and none reverse the loss of vision. Photoreceptor replacement by transplantation is proposed as a broad treatment strategy applicable to all degenerations. Recently, we demonstrated restoration of vision following rod-photoreceptor transplantation into a mouse model of stationary night-blindness, raising the critical question of whether photoreceptor replacement is equally effective in different types and stages of degeneration. We present a comprehensive assessment of rod-photoreceptor transplantation across six murine models of inherited photoreceptor degeneration. Transplantation is feasible in all models examined but disease type has a major impact on outcome, as assessed both by the morphology and number of integrated rod-photoreceptors. Integration can increase (Prph2(+/Δ307)), decrease (Crb1(rd8/rd8), Gnat1(-/-), Rho(-/-)), or remain constant (PDE6ß(rd1/rd1), Prph2(rd2/rd2)) with disease progression, depending upon the gene defect, with no correlation with severity. Robust integration is possible even in late-stage disease. Glial scarring and outer limiting membrane integrity, features that change with degeneration, significantly affect transplanted photoreceptor integration. Combined breakdown of these barriers markedly increases integration in a model with an intact outer limiting membrane, strong gliotic response, and otherwise poor transplantation outcome (Rho(-/-)), leading to an eightfold increase in integration and restoration of visual function. Thus, it is possible to achieve robust integration across a broad range of inherited retinopathies. Moreover, transplantation outcome can be improved by administering appropriate, tailored manipulations of the recipient environment.

[A case of Oguchi disease with disappearance of golden tapetal-like fundus reflex after vitreous resection].

BACKGROUND: Oguchi disease is a form of congenital stationary night-blindness characterized by a golden tapetal fundus reflex. This reflex is known to disappear in the dark-adapted state ("Mizuo-Nakamura phenomenon"). The origin of the reflex is not clear. We report a case of Oguchi disease with the disappearance of the golden tapetal reflex after vitreous resection. CASE: An 80-year-old man was referred for rhegmatogenous retinal detachment of the left eye. Golden tapetal reflex was observed in both eyes. Negative b-wave in the electroretinogram and mutation in the SAG gene indicated Oguchi disease. Pars plana vitrectomy and posterior hyaloid membrane peeling were performed. The tapetal reflex in the all regions of the fundus in the operated eye disappeared after the retina was reattached. The reflex partially recovered 2 years after the operation. CONCLUSION: It is suggested that the change in vitreo-retinal interface after a vitreous operation leads to the disappearance of the reflex. This report presents a hypothesis on the origin of the golden tapetal reflex in Oguchi disease.

Corneal wavefront-guided retreatments for significant night vision symptoms after myopic laser refractive surgery.

PURPOSE: To evaluate the results of corneal wavefront (WF)-guided enhancements in patients with night vision symptoms and significantly high positive spherical aberration (SA) after myopic laser refractive surgery. DESIGN: Noncomparative, interventional case series. METHODS: Twenty-eight eyes of 20 patients with significant night vision symptoms and positive corneal SA (Z(4)(0)) higher than 0.5 microm after myopic laser refractive surgery were included in the study at Vissum-Instituto Oftalmologico de Alicante, Spain. Enhancement surgery was planned to remove residual refractive error and corneal SA (Z(4)(0)) in all cases. All patients underwent corneal WF-guided excimer laser retreatments using the ESIRIS/SCHWIND excimer laser system (Schwind Eye Tech Solutions, Kleinostham, Germany). The main outcome measures were visual symptoms, change in corneal SA (Z(4)(0)), and corneal asphericity (Q-value). RESULTS: Subjective reports of night vision symptoms were improved in all patients. Mean corneal SA (Z(4)(0)) decreased from 0.75 +/- 0.19 microm before surgery to 0.43 +/- 0.42 microm after surgery (P < .001). Mean asphericity in the 4.5-mm zone significantly decreased from 1.02 +/- 1.07 before surgery to 0.52 +/- 0.88 after surgery (P = .008), and the mean asphericity in 8 mm did not change significantly (P = .362). The mean spherical equivalent significantly shifted to hyperopia from -0.22 +/- 1.14 diopters (D) before surgery to 0.33 +/- 0.54 D after surgery (P = .025). CONCLUSIONS: Cornea wavefront-guided retreatment was effective in improving subjective night vision symptoms, reducing corneal SA, and decreasing asphericity in eyes that underwent myopic laser refractive surgery.

A new night vision disturbances parameter and contrast sensitivity as indicators of success in wavefront-guided enhancement.

PURPOSE: To determine the level of success of wavefront-guided repair of night vision disturbances after conventional (Munnerlyn) myopic LASIK using a new parameter to describe higher order aberrations, and to compare the improvements to matched myopic LASIK controls who were symptom-free. METHODS: We developed a single parameter metric to represent raw spherical aberration (RAWS) to functionally describe the cumulative spherical aberration for an eye over a range of physiological pupil sizes. To derive the RAWS parameter, spherical aberration is plotted over pupil analysis zones from 3000 to 6000 microm. The RAWS parameter (unit = microm2) is then equal to the area under the plot. Sixteen eyes treated for night vision disturbances by wavefront-guided repair were each compared to the mean of four matched control eyes (total 64 eyes) treated by aspheric myopic ablation and without night vision disturbances. Contrast sensitivity and RAWs parameter for spherical aberration were determined for each of the repair eyes and control eyes before and after surgery. RESULTS: Following wavefront-guided repair, 76% of eyes were subjectively reported to have night vision disturbances improved by at least 80%. The percentage of eyes within normal contrast range increased from 25% to 80% following wavefront-guided repair (P < .05). For the control eyes, LASIK increased RAWS by 126% (RAWS was 122 microm2 preoperatively and 276 microm2 postoperatively). For the night vision disturbances repair eye group, RAWS at presentation was 104% (563 microm2) above the respective postoperative RAWS control eyes. Following wavefront-guided repair, RAWS was decreased (P < .05) to only 49% (410 microm2) above the postoperative control group. CONCLUSIONS: The RAWS parameter enabled a single digit descriptor of overall higher order aberrations for an eye over the principal physiological pupil range. By comparing RAWS parameter changes in wavefront-guided repair eyes to matched postoperative asymptomatic eyes, we were able to determine the magnitude of the deficit in the symptomatic eyes and the relative efficacy of wavefront-guided repair.