Surgical excision of neovascularization in retinal angiomatous proliferation

Background We report the postoperative outcomes of surgical neovascularization excision in patients with retinal angiomatous proliferation (RAP).Methods Nine eyes of eight patients with RAP who underwent surgical excision of neovascularization were studied. Surgical indications were as follows: RAP diagnosed by fluorescein and indocyanine green angiography, foveal or perifoveal neovascularization, preoperative visual acuity of 0.1 or less, Yannuzzis stage II with detachment of retinal pigment epithelium (RPE) or stage III, and leakage on late-phase fluorescein angiography. After cataract surgery, vitreous surgery and neovascularization excision were conducted, followed by fluid–air or fluid–gas exchange.Results Visual acuity was 0.02–0.1 before surgery and 0.03–0.2 after surgery. Macular hole formation was seen in one eye but did not lead to retinal detachment. In two eyes, subretinal bleeding occurred during excision leading to vitreous bleeding after surgery. Although defects of the RPE and choriocapillaries were observed after surgery, the exudation and bleeding were absorbed.Conclusions In stage II RAP cases with RPE detachment, surgical excision maintains constant postoperative visual acuity but results in defects of RPE and choriocapillaris; therefore, other treatment options should be examined. Surgical excision of stage III RAP seems to be promising, as postoperative visual acuity remains stable after neovascularization removal in those advanced pathologic situations.     

Bilateral midperipheral large drusen and retinal pigment epithelial detachments associated with multifocal areas of choroidal neovascularization: a histopathologic study

PURPOSE: The ocular histopathologic features of a patient with bilateral multiple midperipheral areas of choroidal vascularization, large drusen, and detachments of the retinal pigment epithelium (RPE) are presented. METHODS: The eyes were obtained at autopsy and fixed in 4% buffered formaldehyde. Serial sections through the macula area and inferior segments were prepared. Light as well as electron microscopy was performed. RESULTS: Microscopic examination disclosed numerous large drusen measuring up to 200 micro m in height and 280 micro m in diameter and areas of serous RPE detachments in the midperiphery of both eyes. Some of the large drusen had choroidal vascularization. Areas of sub-RPE neovascularization that measured up to 6.5 mm in diameter were present in the midperiphery of both eyes. The choroidal origin for neovascularization was evident in 10 areas. A 1-mm area of hemorrhagic detachment of the RPE contiguous with choroidal neovascularization (CNV) was present in the immediate postequatorial area temporally in the left eye. No drusen, basal deposit, or CNV was present in the macular area. CONCLUSION: Multifocal midperipheral RPE detachments and CNV can occur in the absence of significant age-related macular disease.     

Dark adaptation in age-related macular degeneration: relationship to the fellow eye

BACKGROUND: Abnormalities of dark adaptation have been documented in patients with age-related macular degeneration (AMD), but the relationship with the various forms of this disorder has not been studied systematically. METHODS: Dark-adapted retinal sensitivities and kinetics of dark adaptation were studied using a Humphrey visual field analyzer adapted for these purposes in patients over 64 years of age. One eye per patient was studied. Study eyes had a normal visual acuity and macular drusen only. The fellow eye was categorized as follows: group I, pigment epithelial detachments and tears of the retinal pigment epithelium (RPE); group II, choroidal neovascularization; and group III, drusen only. The results of psychophysical tests of the study eyes (group I and II and one eye of group III patients) were compared with one another and with older patients without evidence of AMD (group IV). RESULTS: Retinal sensitivity was found to be most consistently abnormal nearest the fovea. The time course of dark adaptation was prolonged beyond 45 min in 10/11 patients (91%) in group I, 6/10 patients (60%) in group II, and 6/10 (60%) in group III and 1/11 (9%) in group IV. CONCLUSION: In a high proportion of patients with visual loss from AMD in one eye, the fellow eye shows abnormal dark adaptation. These changes appear to be most pronounced in patients with detachments of the RPE in the fellow eye.     

Age-related macular disease in a 91-year-old patient: Histologic findings

Age-related macular degeneration in the eye of a 91-year-old man was studied histologically. Typical of this disease, which manifests as death of central photoreceptors, were dystrophic changes of the retinal pigment epithelium (RPE) and neural retina. Also typical were increased drusen deposits, which accumulated between the RPE basement membrane and the inner layer of Bruch's membrane, and choroidal neovascularization. We histologically observed and demonstrated a subclinical neovascularization that fluorescein angiography did not.     

Thrombospondin-1 Expression in RPE and Choroidal Neovascular Membranes

Introduction Age-related macular degeneration (AMD) s the leading cause of blindness in the West or individuals more than 50 years of age[1-3].Severe visual loss in the late stages of AMD most commonly results from choroidal neovas- cularization (CNV), a process characterized by the growth of new vessels from the choriocapil- laris through Bruch′s membrane. These new vessels are prone to leakage and bleeding and may be associated with detachment of the retinal pigment epithelium (RPE). …     

Inhibition of proliferation,migration and tube formation of choroidal microvascular endothelial cells by targeting HIF-1α with short hairpin RNA-expressing plasmid DNA in human RPE cells in a coculture system

BACKGROUND: Retinal pigment epithelial (RPE) cells and choroidal microvascular endothelial cells (CECs) are the main cells involved in choroidal neovascularization (CNV), and hypoxia plays an important role in CNV formation via hypoxia inducible factor 1 (HIF-1). Our aim was to evaluate the role of HIF-1 in human RPE cells with regard to proliferation, migration and tube formation of CECs under hypoxia. METHODS: RPE cells were cultured under chemical hypoxia induced by 200 muM CoCl(2), and RNA interference (RNAi) technique was used to knock down HIF-1alpha gene in RPE cells. mRNA and protein expression of HIF-1alpha and VEGF in RPE cells were investigated by real-time RT-PCR and Western blot. Three kinds of coculture models were used to observe the effects of RPE cells transfected by short hairpin RNA (shRNA)-expressing plasmid DNA (pDNA) (pshHIF-1alpha) on the proliferation, migration and tube formation of CECs respectively. RESULTS: Transfection of shRNA-expressing pDNA targeting HIF-1alpha to RPE cells resulted in the knock down of HIF-1alpha gene and reduction of the corresponding mRNA and protein of HIF-1alpha and VEGF under hypoxia. Consequently, the proliferation, migration and tube formation of CECs were significantly inhibited by the knocked-down RPE cells compared with the control in the coculture system. The proliferation rates of CECs decreased by 40.2%, 36.6% and 36.8% on days 3, 4 and 5 respectively. Migration reduced by 49.6% at 5 h, and tube formation decreased by 40.4% at 48 h. CONCLUSION: RNAi of HIF-1alpha in RPE cells can inhibit angiogenesis in vitro and provide a possible strategy for treatment of choroidal neovascularization diseases by targeting HIF-1alpha.     

Reduced foveolar choroidal blood flow in eyes with increasing AMD severity

PURPOSE: In an earlier study, the authors reported that foveolar choroidal blood flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the choroidal circulatory changes in patients with AMD, the relationship between ChBFlow and fundus features associated with increased risk of choroidal neovascularization (CNV) were investigated. METHODS: The study included 26 control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of 123 patients with AMD. The AMD study eyes were divided into three groups according to increasing risk for development of CNV: (1) drusen > or =63 microm, no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; (2) drusen > or =63 microm, RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory parameters were assessed by analysis of variance (ANOVA) and test of linear trend. RESULTS: Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk for CNV (linear trend, P < 0.05). The lowest circulatory parameters were observed in the eyes with the highest risk for CNV development. Trends for ChBVel and ChBFlow were still significant after adjustment for multiple factors. CONCLUSIONS: There is a systematic decrease in choroidal circulatory parameters with an increase in the severity of AMD features associated with risk for the development of CNV, suggesting a role for ischemia in the development of CNV.     

Macular diseases in the elderly person

Macular diseases in the elderly, such as age-related macular degeneration, idiopathic senile macular hole and epiretinal membrane of the macular area were studied. In 75 normal subjects aged from 20 to 78 years, retinal sensitivity in the central 10 degree visual field were examined using automated static quantitative perimetry. For background luminance of 31.5 asb, a significant reciprocal correlation was demonstrated between individual mean sensitivity and age. The influence of age on the decrease in sensitivity was proved to differ according to different test locations. To enhance contrast, an image processing procedure was applied for fluorescein angiographs of age-related pathologies which resulted in better recognition of age-related RPE pathologies were recognized. The senile disciform macular degeneration (SDMD) study group sponsored by the Ministry of Health and Welfare performed an epidemiological survey to estimate the number of patients with SDMD. The epidemiological estimation was 6,000 to 13,000 patients in the entire Japanese population. 133 eyes of uni- or bi-lateral senile macular degeneration without choroidal neovascularization and 156 opposite eyes of patients with unilateral SDMD were followed-up for choroidal neovascularization development. Choroidal neovascularization development was confirmed in 15 eyes, 5.2%. In 13 of the 15 eyes, choroidal neovascularization was proved to develop through serous RPE detachment. Also, serous drusen were shown to be to predisposed to choroidal neovascularization through serous RPE detachment. Therefore, it was concluded that senile macular degeneration should be classified into the atrophic form, predisciform or intermediate form and disciform form. In the author's previous paper, it was reported that the navel-like lesion would be a macular lesion predisposing to a senile macular hole. 49 opposite eye of patients with one eye affected by a macular hole were follow-up for macular hole development. At the initial examination, the navel-like lesion was observed in 5 of the 49 eyes. During the course of observation, navel-like lesions developed in one of the other 27 eyes with other abnormalities and in 4 of the 17 eyes without any abnormality. Finally, macular holes developed in 11 of the 49 eyes; in 10 eyes with a navel-like lesion and one eye with another abnormality. We found a 17 year old female Japanese monkey with pre-macular holes in both eyes and clinicopathological correlative study was carried out. In her right eye, photoreceptor cell loss at the foveola, circumferential retinal detachment around the area of cell loss, cystoid spaces in the detached retina, and very thin residual tissue covering the foveolar lesion were observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characteristic Findings of Optical Coherence Tomography in Retinal Angiomatous Proliferation

Purpose

To identify the unique pathologic findings of retinal angiomatous proliferation (RAP) in optical coherence tomography (OCT).

Methods

Retrospectively, 29 eyes of 25 patients with age-related macular degeneration and complicated RAP were analyzed. All 29 eyes had choroidal neovascularization (CNV) in the area of pigment epithelial detachment (PED) or adjacent to it, which was visible with fluorescein angiography or indocyanine green angiography. Cross-sectional images were obtained by OCT scanning through the CNV lesions.

Results

Six distinctive findings of OCT included drusen (100%), inner retinal cyst (80%), outer retinal cyst (68%), fibrovascular PED (84%), serous retinal detachment (40%), and PED (68%).

Conclusions

Through analysis of OCT findings, we revealed six different types of lesions distinctive of RAP which may provide helpful diagnostic information for subsequent treatment and predicting the prognosis of RAP.     

Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization

Purpose. Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1α on ocular NV. Methods. Conditional HIF-1α knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1α floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models. Results. HIF-1α levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF-1α KO mice. Under normal conditions, the HIF-1α KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1α KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1α and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1α in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area. Conclusions. RPE-derived HIF-1α plays a key role in CNV, but not in ischemia-induced retinal NV.     

Retinal angiomatous proliferation in age-related macular degeneration

BACKGROUND: Angiomatous proliferation in ARMD originates from the retina and extends into the subretinal space. Retinal angiomatous proliferation (RAP) is diagnosed with angiography. This study investigates the characteristics of RAP in optical coherence tomography (OCT) and correlates them with clinical and fluorescein angiographic findings. METHODS: 327 consecutive patients with age-related macular degeneration (ARMD) were retrospectively examined using a standardised protocol. The protocol included best corrected visual acuity (BCVA), binocular ophthalmoscopy, fundus photography, fluorescein angiography (FAG) and OCT. The OCT and angiographic findings were graded in 3 RAP stages. RESULTS: 32 of 327 (9.79 %) patients (45 eyes) had RAP. The age ranged from 56 to 90 years (median: 79 years). 9 eyes presented RAP stage I, 23 stage II and 13 stage III. BCVA ranged from 0.01 to 0.7 (median: 0.2). OCT foveal minimum was 136 to 722 microns (median: 327). 33 (73 %) eyes showed a detachment of retinal pigment epithelium (RPE). Macular oedema was found in 43 (96 %) eyes. Cystoid macular oedema was seen in 36 (80 %) eyes. In stage II, 22 eyes (96 %) showed an RPE detachment, in stage III 11 eyes (85 %). 11 (85 %) eyes in stage III showed retinal-choroidal anastomosis. CONCLUSIONS: RAP was found in 9.79 % of the patients with ARMD. The OCT is helpful in detection of RPE detachment, macular oedema and cystoid changes in RAP. RAP and retinal-choroidal anastomosis should be identified because of the possibly poor prognosis.     

Photodynamic therapy with verteporfin for retinal angiomatous proliferation

Purpose The aim of this study was to evaluate the results of photodynamic therapy (PDT), using verteporfin, for subfoveal neovascular age-related macular degeneration (ARMD) with retinal angiomatous proliferation (RAP) with pigment epithelial detachment (PED) and/or choroidal neovascularization (CNV).Methods In this non-comparative, consecutive, interventional, case series, the data on 21 eyes (19 with stage 2 and two with stage 3 RAP) of 20 patients were reviewed. Serous PED occupied more than 50% of the lesion in 19 eyes. PDT was performed as per TAP protocol. Biomicroscopy and fluorescein and indocyanine-green angiography were performed to evaluate anatomical results and need for retreatment. Changes from baseline in best-corrected visual acuity (BCVA), and complications, were assessed.Results A mean of 3.5±0.9 treatments was performed. After 13.7±2.2 months, mean BCVA decreased from 20/80 to 20/174 (P=0.0063). In six eyes (28.6%) BCVA remained stable, whereas in 15 eyes (71.5%) it decreased. Occlusion of RAP and flattening of PED was observed in three (14.2%) eyes, conversion to disciform lesion in one (4.7%), and persistence of PED in 11 eyes (52.3%). One eye (4.7%) evolved to haemorrhagic PED, and one (4.7%) toward stage 3 RAP. A tear in the retinal pigment epithelium (RPE) was observed in four eyes (19%). Eleven (52.3%) showed progression of leakage, six moderate leakage (28.6%), and three (14.2%) absence of leakage.Conclusions Timely PDT with verteporfin in the early stages in eyes with smaller lesions has the potential for a beneficial effect on vision, whereas it might worsen the natural course of larger lesions, with most eyes undergoing enlargement, disciform transformation or RPE tear.Presented in part as a paper at the American Academy of Ophthalmology Annual Meeting, Anaheim, California, 15–18 November 2003The authors have no financial interest in this study     

Retinal Angiomatous Proliferation in an Eye with Cuticular Drusen

Purpose

To report the presence of retinal angiomatous proliferation (RAP) in an eye with cuticular drusen detected by fluorescein and indocyanine green angiography by confocal scanning laser ophthalmoscopy and by spectral-domain optical coherence tomography (SD-OCT).

Methods

Case report of a 65-year-old Japanese woman with cuticular drusen.

Results

At her first ophthalmic examination, her visual acuity was 20/20 in both eyes. An ophthalmoscopy showed many small subretinal pigment epithelial deposits in both eyes. These deposits had a ‘saw-tooth pattern’ in the SD-OCT images. During the follow-up examination, retinal hemorrhages were observed, and fluorescein angiography showed a ‘stars-in-the-sky’ appearance and intraretinal neovascularization. The patient was diagnosed with cuticular drusen associated with RAP.

Conclusion

We suggest that the cuticular drusen were associated with RAP, so periodic follow-up examinations are needed for patients with cuticular drusen for the early detection and treatment of RAP.Key Words: Cuticular drusen, Basal laminar drusen, Retinal angiomatous proliferation, Spectral domain optical coherence tomography     

Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization

PURPOSE: Pigment epithelium-derived factor (PEDF) is a protein produced by the retinal pigment epithelial (RPE) cells. Recent studies have implicated PEDF in activities that are inhibitory to angiogenesis. In this study, the expression of PEDF was investigated in normal rat eyes and in eyes with experimentally induced choroidal neovascularization and compared with the expression of vascular endothelial growth factor (VEGF). METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. At intervals of up to 2 weeks after photocoagulation, the eyes were removed and prepared for in situ hybridization and immunohistochemical study. In situ hybridization was performed with digoxigenin-labeled PEDF riboprobes. Protein expression of PEDF and VEGF was studied immunohistochemically. RESULTS: In normal adult rat eyes, PEDF mRNA was observed mainly in the corneal epithelial and endothelial cells, lens epithelial cells, ciliary epithelial cells, retinal ganglion cells, and the RPE cells. During the development of choroidal neovascularization, PEDF mRNA, PEDF protein, and VEGF protein were strongly detected in many cells within the laser lesions at 3 days after photocoagulation, after which levels gradually declined. However, PEDF was still expressed in the RPE cells that proliferated and covered the neovascular tissues at 2 weeks, whereas VEGF protein was weakly expressed in endothelial cells in choroidal neovascularization. CONCLUSIONS: PEDF is expressed in different cell types of normal rat eyes. The expression of PEDF was detected in the choroidal neovascular tissues induced by photocoagulation, and these findings suggest that PEDF may modulate the process of choroidal neovascularization.     

Combining surgical ablation of retinal inflow and outflow vessels with photodynamic therapy for retinal angiomatous proliferation

PURPOSE: To evaluate short-term efficacy of combining surgical ablation of retinal inflow and outflow vessels and photodynamic therapy (PDT) for stage 3 retinal angiomatous proliferation (RAP). DESIGN: Prospective interventional case series. METHODS: Five eyes (five patients) underwent surgical ablation of inflow and outflow vessels and PDT for stage 3 RAP. RESULTS: Inflow and outflow vessels were ablated in four eyes, and only inflow was ablated in one eye. In four eyes starting PDT within six weeks of surgical ablation, choroidal neovascularization (CNV) disappeared or shrank after one PDT session (three months follow-up). However, CNV enlarged again in three of the four (final follow-up) because of reperfusion from newly formed inflow vessels. In one eye starting PDT seven months after ablation, a new retinal inflow vessel feeding the CNV appeared by the time of the first PDT session. The CNV continued to expand, despite two PDT sessions. CONCLUSIONS: Combining surgical ablation and PDT was not useful on account of a high frequency of reperfusion from retinal inflow vessels.     

A model of subretinal neovascularization in the pigmented rat

We produced krypton laser photocoagulation lesions of mild to moderate whiteness in the posterior retinas of one eye of 23 pigmented rats, and identical appearing argon laser burns in the fellow eyes. We observed foci of subretinal neovascularization, histopathologically markedly similar to that which occurs in several human retinal diseases, in the krypton laser treated eyes of 6 of the 14 rats that were followed for one to three months after photocoagulation. No such lesions were observed in the argon laser treated fellow eyes, nor in krypton or argon laser treated eyes examined earlier than one month after photocoagulation. The photocoagulation damaged only the choriocapillaris, the retinal pigment epithelium (RPE), and the photoreceptor layer. In the acute lesions, we did not observe ruptures in Bruch's membrane. The neovascularization was surrounded by multiple layers of RPE cells, a histopathologic finding that has also been reported in some human eyes with subretinal neovascularization in age-related macular degeneration. These observations suggest that the RPE cells may be modifying the proliferative behavior of adjacent choroidal capillaries. This model differs from previous models of subretinal neovascularization in primates, and may be useful for additional studies of this important pathological process.     

Drusen characteristics in patients with exudative versus non-exudative age-related macular degeneration

The drusen characteristics of 38 eyes from 38 patients with bilateral drusen associated with age-related macular degeneration (AMD) were compared in a masked fashion to 89 fellow eyes from 89 patients with unilateral exudative AMD (disciform scarring or choroidal neovascularization). The average age of the drusen group (67.4 years) was significantly less (P = 0.01) than the average age of the unilateral exudative group (72.6 years). Multiple logistic regression was used to compare the drusen characteristics in the two groups, controlling for the age and sex of the patients. Among patients 75 years of age and younger, patients with confluent drusen had an increased risk of having a fellow eye with exudative AMD compared with patients without confluent drusen. Among patients older than 75 years of age, confluent drusen did not significantly differentiate the two study groups, although confluent drusen in this older age group were more often associated with the bilateral drusen group. Focal hyperpigmentation of the retinal pigment epithelium was also associated with the unilateral exudative group. These drusen characteristics should be evaluated in future prospective studies designed to determine which eyes with drusen are at greatest risk for developing the blinding complications of choroidal neovascularization.     

Recurrence after surgical ablation for retinal angiomatous proliferation

PURPOSE: To report the frequency of recurrence of retinal angiomatous proliferation (RAP) lesions after surgical ablation. METHODS: Seven eyes of seven consecutive patients with stage II RAP underwent surgical ablation of retinal feeder and draining vessels of RAP lesions. These eyes were examined with visual acuity testing, biomicroscopic slit-lamp fundus examination, fluorescein and indocyanine green angiographies, and optical coherence tomography before and after surgery. RESULTS: Between 2 months and 13 months after surgical ablation, all 7 eyes (100%) had lesion recurrence with exudative and/or hemorrhagic manifestations such as macular edema, serous detachment of the sensory retina, or pigment epithelial detachment. Retinal feeding and draining vessels were recanalized (six eyes) or newly developed (one eye) in communication with recurrent intraretinal neovascularization. CONCLUSIONS: After surgical ablation for stage II RAP, all seven eyes had recurrence of the RAP lesions. This treatment may be ineffective for RAP. Further study of this surgical technique is necessary before recommending it for the treatment of RAP.     

Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment.DESIGN: Randomized controlled clinical trial.METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 micro diameter, pericentral 1500 micro ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (> or = 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes.RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P =.00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm(2) compared with 14.8 laser-induced lesions and 0.35 mm(2) area of RPE change in eyes without major drusen reduction (P =.0001 and P =.0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes.CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.