Effect of cataract surgery in patients with neovascular age-related macular degeneration: further evidence from disciform scars

Purpose

To evaluate the effect of cataract surgery on disease activation and visual outcomes in neovascular age-related macular degeneration (AMD).

Methods

In this retrospective case–control study, study arm consisted of neovascular AMD patients, who underwent phacoemulsification surgery. Patients did not have any disease activation at least 6 months before the inclusion, and all had at least 12-month follow-up thereafter. Control group consisted of phakic patients, who did not undergo eye surgery during the study period. Primary outcomes were the presence of the disease activation and the change in best-corrected visual acuity (BCVA).

Results

A total of 114 neovascular AMD patients [55 (48%) in exudative group and 59 (52%) in disciform group] were included. Preoperative logMAR BCVA was significantly improved after cataract surgery [0.8 (0.6–1.0) vs. 0.4 (0.4–0.7), P < 0.001 in exudative AMD; 1.85 (1.1–1.9) vs. 1.09 (0.8–1.9), P = 0.001 in disciform scar], but this improvement was not maintained during the study period in patients with both exudative AMD and disciform scar [0.6 (0.3–1.1), P = 0.313 in exudative AMD; 1.30 (1–1.9), P = 0.03 in disciform scar]. The incidence of disease activation was not statistically significant between surgery and control groups in patients with exudative AMD [5 (25%) patients in surgery group and 8 (22%) patients in the control group, P = 0.886, Cox proportional hazards regression analysis]. In disciform scar, disease activation was observed in 4 (17%) patients in the surgery group; however, no patient in the control group had disease activation (P = 0.009, HRs could not be estimated, 95% CI 0.001–43.49, Cox proportional hazards regression analysis).

Conclusion

Cataract surgery has benefit on early postoperative visual improvement in patients with neovascular AMD. The incidence of disease activation was not affected after surgery in exudative AMD.

     

Morphometric analysis of the macula in eyes with disciform age-related macular degeneration

PURPOSE: To evaluate the extent of neural cell death in eyes with disciform age-related macular degeneration. METHODS: Six eyes with disciform degeneration at various stages and five age-matched control eyes were selected for morphometric analysis using digitized light microscopic images. Disciform scars were classified as subneurosensory retinal, subretinal pigment epithelial, or combined lesions. The nuclei of the ganglion cell, inner nuclear, and outer nuclear layers were counted in contiguous 100 microm segments spanning a distance from 1,500 microm nasal to 1,500 microm temporal to the fovea. RESULTS: The outer nuclear layer was most severely attenuated in eyes with disciform scars, demonstrating a 69.4% reduction in cell number relative to control eyes. A loss in retinal ganglion cells (by 7.3%) and an increase in inner nuclear layer cells (by 10%) were observed, but these changes were not significant. Photoreceptor loss was most pronounced when the disciform scar was not covered by the retinal pigment epithelium. CONCLUSION: The nuclei of the outer nuclear layer are significantly attenuated in eyes with disciform age-related macular degeneration, while the ganglion cell and inner nuclear layers are relatively preserved. These findings suggest that replacement of outer nuclear function, by either retinal transplantation or implantation of the intraocular retinal prosthesis, might be a feasible therapeutic option for patients with this condition.     

Morphologic characteristics of disciform scarring after radiation treatment for age-related macular degeneration

OBJECTIVE: To investigate the influence of radiation therapy on the development of disciform lesions in patients with age-related macular degeneration (AMD). DESIGN: A prospective, nonrandomized, comparative trial (patient self-controlled). PARTICIPANTS: Forty eyes with exudative AMD involving the central fovea in 40 consecutive patients were enrolled in this study. INTERVENTION: Radiation was administered to the posterior pole with an 8-mV photon beam from a linear accelerator. A dose of 14.4 Gy, 1.8 Gy per day, five fractions per week was delivered through a single port. MAIN OUTCOME MEASURES: The visual acuity and the morphologic characteristics, demonstrated by fundus photography, fluorescein, and indocyanine green angiography, were investigated before treatment and every 3 months after treatment over a period of 24 months. In 10 patients with bilateral disease the disciform lesions were compared. RESULTS: Twenty five patients could be followed regularly over the period of 24 months. The disciform lesions occurring after radiation were classified in three types. Type I (10 patients) was characterized by being smaller than 2 DD in size, with little fibrotic tissue underneath the retina, but pronounced retinal pigment epithelial changes. Type II (seven patients) showed extensive growth of the choroidal neovascularization (CNV) extending to and beyond the arcades with angiographically active loops in the peripheral parts. Eight patients had type III lesions develop characterized by a size greater than 2 DD but fewer than 6 DD and by a different amount of fibrotic tissue, hemorrhage, and lipid. Type I scarring was significantly associated with occult CNV without pigment epithelial detachments, whereas type II scarring was associated with classic CNV at the initial presentation (P<0.05). CONCLUSIONS: Although no severe side effects have been reported after radiation therapy for AMD, a subgroup of patients may experience extensive growth of CNV after radiation, causing greater functional damage than occurs spontaneously.     

Senile disciform macular degeneration in the second eye.

Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk of developing disciform degeneration in the second eye.     

Senile disciform macular degeneration and smoking

We studied the smoking habits of 114 patients with senile disciform degeneration of the macula. The mean age at onset of blindness in the first eye was 64 years in those currently smoking; this was significantly less than the mean age in those who had never smoked (71 years). We advise all patients with disciform degeneration to stop smoking.     

The time pattern of bilateral exudative age-related macular degeneration

PURPOSE: To study time patterns in bilateral exudative age-related macular degeneration (AMD) and the pattern of drusen before and after the onset of exudative AMD. MATERIAL AND METHODS: Out of 2220 individuals in the Icelandic genetic study of AMD, 151 had bilateral exudative AMD. We searched for previous records in the Icelandic University Retina Unit. For the 65 patients with a fluorescein angiography record of both eyes, we established the time between the onset of disease in each eye. For the 53 patients with colour fundus photographs of the latter eye taken prior to the occurrence of exudative disease, we graded the drusen before and after the onset of exudative AMD in the second eye. RESULTS: The time interval between the onset of exudative AMD in the first and second eyes was 2.5 years (95% CI: 1.8-3.2; n = 65) and the median was 1.8 years. In 82% of cases the second eye was affected within 4 years. Soft drusen in the macula were found in 95% of eyes that later developed exudative disease (n = 53). Soft and hard drusen decreased in number in the central macula following the development of exudative disease. CONCLUSIONS: Bilateral exudative AMD develops within a few years in both eyes. Drusen are less visible following the onset of exudative AMD in the second eye.     

Macular lesions predisposing to senile disciform macular degeneration.

Senile disciform macular degeneration (SMD) is a neovascular/exudative form of age-related macular degeneration (AMD). In this study 340 eyes were followed up to assess the progression of SMD. The 340 eyes consisted of two groups. Group 1 was composed of 157 eyes with age-related macular changes other than choroidal neovascular membrane. Group 2 was made up of the contralateral eyes of 183 unilateral SMD eyes. Average ages were 61 and 64 in groups 1 and 2, respectively, and respective follow-up periods were 44 and 52 months. Choroidal neovascular membrane developed in 12 eyes in group 1 (7.6%) and in 19 eyes in group 2 (10.4%), a total of 31 eyes (9.1%). Retinal pigment epithelium (RPE) detachment was found as a predisposing lesion in 25 of these 31 eyes. Choroidal neovascular membrane developed in 12 of the 24 eyes with large RPE detachments. In 3 eyes neovascular membrane developed from an RPE detachment which had evolved from soft drusen. There were 3 eyes among the 62 eyes with soft drusen in which neovascular membrane developed directly from soft drusen. Based on these results, we classified AMD into 3 types; 1) atrophic, 2) predisciform, which includes RPE detachment and soft drusen, and 3) SMD.     

Transplantation of RPE in age-related macular degeneration: Observations in disciform lesions and dry RPE atrophy

A study was carried out to investigate whether human RPE allografts are tolerated or rejected in the subretinal space and to determine the feasibility of RPE transplantation in subjects with age-related macular degeneration (AMD). Methods: Patches of human fetal RPE (13–20 weeks of gestational age) were transplanted into the subretinal space of five patients after surgical removal of subfoveal fibrovascular membranes, and to four subjects with dry geographic atrophy. Suspensions of RPE cells were transplanted to four other patients with nonexudative AMD. Results were evaluated with clinical ophthalmological examination, SLO microperimetry and fluorescein angiography over 8–20 months. Results: In disciform lesions, RPE transplants developed macular edema and fluorescein leakage concomitant with gradual reduction of visual acuity, implying host-graft rejection, over 1–6 months. In geographic atrophy, three of four transplants showed little change in shape and size after 12 months (one transplant was slowly rejected). In non-exudative AMD, RPE suspension transplants showed no evidence of rejection and were associated with the disappearance of drusen; visual acuity remained stable and SLO microperimetry confirmed retinal function over the transplanted area. Conclusion: Human RPE allografts are not invariably rejected in the subretinal space without immunosuppression. The rejection rate is lower in nonexudative than in neovascular AMD. An intact blood-retinal barrier is likely to protect against rejection. It is technically feasible to transplant human RPE into the submacular space without adversely affecting visual function in nonexudative AMD over relatively long periods of timeThis work was supported by grants from the Swedish Medical Research Council (B96-12X-11561-01A) and the Crown Princess Margareta Foundation, Stockholm, Sweden.     

VEGF in age-related macular degeneration. Part II. VEGF inhibitors use in age-related macular degeneration treatment

Wet AMD remains a therapeutic challenge. VEGF inhibitors are new promising group of medical agents undergoing advanced clinical trials. Oncology is the main specialty using anti-VEGF therapy. Two agents were designed from the beginning as ophthalmologic medicines. These are pegaptanib and ranibizumab. In the paper there is mechanism, efficacy and safety data presented, especially coming from multi-center randomized clinical trials. Monoclonal VEGF-antibodies (ranibizumab and bevacizumab) seem to be most effective in wet AMD treatment. Because of important physiological VEGF role long-term observation is needed to confirm safety of VEGF inhibition.     

老年黄斑变性中感光细胞的凋亡

目的 探讨细胞凋亡在老年黄斑病变性感光细胞死亡中的作用。方法 对１６只老年黄斑变性眼的黄斑部视网膜组织进行ＴＵＮＥＬ技术（ＴＤＴ－ｍｅｄｉａｔｅｄｂｉｏｔｉｎ－ｄＵＴＰｎｉｃｋ－ｅｎｄｌａｂｅｌｌｉｎｇ）和病理组织学研究。结果 本组中６只眼的黄斑病有细胞凋亡的特征性改变,分散排列的感光细胞核ＤＮＡ片断化。结论 细胞凋亡是老年黄斑变性中感光细胞死亡的一个重要机理。     

炎症与年龄相关性黄斑变性

近年来炎症与年龄相关性黄斑变性（AMD）的关系受到关注，主要包括与炎症相关的免疫分子与AMD的关系，如补体系统和炎症相关基因、单核细胞趋化蛋白（MCP）、C反应蛋白（CRP）等，以及炎症与AMD病理改变的关系如视网膜色素上皮细胞（RPE）损伤、玻璃膜疣以及脉络膜新生血管形成（CNV）等。