K. Z. Aung

Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage

Age‐related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruchs membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure. Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR. In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 ran, ApoEnull untreated 890 ± 60 nm, C57B16J 606 ± 43 nm), with the expression of matrix metalloproteinase‐2 and ‐3 increased (>260%). Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.—Jobling, A. I., Guymer, R. H., Vessey, K. A., Greferath, U., Mills, S. A., Brassington, K. H., Luu, C. D., Aung, K. Z., Trogrlic, L., Plunkett, M., Fletcher, E. L. Nanosecond laser therapy reverses pathologic and molecular changes in age‐related macular degeneration without retinal damage. FASEB J. 29, 696‐710 (2015). www.fasebj.org

Role of Flicker Perimetry in Predicting Onset of Late-Stage Age-Related Macular Degeneration

OBJECTIVE To investigate the longitudinal changes in flicker perimetry in patients with age-related macular degeneration (AMD) as the condition progresses from early AMD to geographic atrophy (GA) or choroidal neovascularization (CNV). METHODS Patients with AMD and control subjects were recruited from a longitudinal study of retinal function in early AMD consisting of 187 participants. Only those who completed at least 4 consecutive, 6-monthly flicker perimetry tests were selected for this study. Study groups consisted of everyone who went on to develop GA (n = 16) or CNV (n = 5), controls (n = 24), and the high-risk, early- AMD participants whose eyes did not progress to GA or CNV (drusen >125 μm; n = 18). The flicker sensitivity was determined, and its rate of change during the 18 months before the clinical detection of late AMD was calculated. RESULTS Eyes that went on to develop GA or CNV had a significantly reduced mean (SD) flicker sensitivity in the months before clinical detection of GA (15.8 [5.6] dB) or CNV (19.1 [3.8] dB) compared with control eyes (22.9 [3.0] dB) (P < .001) and with eyes that did not progress to GA or CNV (21.4 [3.4] dB) (P < .001). The rate of change in flicker sensitivity was significantly increased in GA eyes (-0.07 dB/mo) (P < .001) but not in CNV eyes (0.006 dB/mo) (P = .56) compared with the control eyes (-0.003 dB/mo). CONCLUSIONS Flicker sensitivity is reduced in eyes that go on to develop late AMD. The rate of change in flicker sensitivities over time was particularly useful in predicting eyes and areas within the eye that subsequently develop GA.

Static and flicker perimetry in age-related macular degeneration.

PURPOSE The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. METHODS This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. RESULTS The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] < 0.001) and noncentral geographic atrophy (GA; P[static and flicker] < 0.001) had significant reductions in static and flicker sensitivities compared to normal eyes. Static (β-coefficient -1.59, 95% confidence interval [CI] -4.78-1.60) and flicker (β-coefficient -1.29, 95% CI -4.66-2.08) sensitivities declined at a similar rate in eyes that showed clinical signs of progression. CONCLUSIONS Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 μm are present, but before the development of late AMD.