Elevated Fundus Autofluorescence in Monkeys Deficient in Lutein, Zeaxanthin, and Omega-3 Fatty Acids.

PURPOSE: We quantified fundus autofluorescence (FAF) in the nonhuman primate retina as a function of age and diets lacking lutein and zeaxanthin (L/Z) and omega-3 fatty acids. METHODS: Quantitative FAF was measured in a cross-sectional study of rhesus macaques fed a standard diet across the lifespan, and in aged rhesus macaques fed lifelong diets lacking L/Z and providing either adequate or deficient levels of omega-3 fatty acids. Macular FAF images were segmented into multiple regions of interest, and mean gray values for each region were calculated using ImageJ. The resulting FAF values were compared across ages within the standard diet animals, and among diet groups and regions. RESULTS: Fundus autofluorescence increased with age in the standard diet animals, and was highest in the perifovea. Monkeys fed L/Z-free diets with either adequate or deficient omega-3 fatty acids had significantly higher FAF overall than age-matched standard diet monkeys. Examined by region, those with adequate omega-3 fatty acids had higher FAF in the fovea and superior regions, while monkeys fed the diet lacking L/Z and omega-3 fatty acids had higher FAF in all regions. CONCLUSIONS: Diets devoid of L/Z resulted in increased retinal autofluorescence, with the highest values in animals also lacking omega-3 fatty acids. The increase was equivalent to a 12- to 20-year acceleration in lipofuscin accumulation compared to animals fed a standard diet. Together these data add support for the role of these nutrients as important factors in lipofuscin accumulation, retinal aging, and progression of macular disease.

CORRELATION BETWEEN SUBFOVEAL CHOROIDAL THICKNESS AND FOVEAL THICKNESS IN THALASSEMIC PATIENTS.

PURPOSE: To assess the impact of two iron chelation modalities in thalassemic patients on foveal and subfoveal choroidal thickness. METHODS: The study included 60 ß-thalassemia major patients. They included 30 patients on oral deferasirox after a period of subcutaneous deferoxamine (Group 2) and 30 patients on subcutaneous deferoxamine (Group 3). Thirty age- and sex-matched healthy children were included as a control group (Group 1). All participants underwent a complete ophthalmologic evaluation and Spectral Domain Optical Coherence Tomography. RESULTS: Age, gender, intraocular pressure, best-corrected visual acuity, and refraction were not statistically different between the three studied groups. Ferritin level, pretransfusion hemoglobin, serum iron, and duration of thalassemia were not statistically different between the two thalassemic groups. Foveal thickness in Group 1 (225.15 ± 17.35 µm) was statistically higher than in Group 2 (210.53 ± 21.73 µm) (P < 0.001) and Group 3 (200.15 ± 7.34 µm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P = 0.001). Subfoveal choroidal thickness in Group 1 (279.70 ± 32.54 µm) was statistically higher than in Group 2 (255.80 ± 19.20 µm) (P < 0.001) and Group 3 (248.28 ± 20.43 µm) (P < 0.001). It was statistically higher in Group 2 than in Group 3 (P < 0.05). CONCLUSION: Thalassemic patients can develop a significant decrease in foveal thickness because of the inevitable use of chelation therapy. Deferoxamine as a chelating agent can affect foveal thickness more than the oral form (deferasirox).

The relationship of central foveal thickness to urinary iodine concentration in retinitis pigmentosa with or without cystoid macular edema.

IMPORTANCE: Current treatments for cystoid macular edema (CME) in retinitis pigmentosa (RP) are not always effective, may lead to adverse effects, and may not restore visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce CME in RP. OBJECTIVE: To determine whether central foveal thickness (CFT) in the presence of CME is related to dietary iodine intake inferred from urinary iodine concentration (UIC) in nonsmoking adults with RP. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional observational study of 212 nonsmoking patients aged 18 to 69 years referred to our institution for RP with visual acuity of no worse than 20/200 in at least 1 eye. EXPOSURE: Retinitis pigmentosa with or without CME. MAIN OUTCOMES AND MEASURES: With the eye as the unit of analysis, the relationship of log CFT measured by optical coherence tomography to UIC measured from multiple spot samples and represented as a 3-level classification variable (<100, 100-199, and ≥200 µg/L), assigning greater weight to patients with more reliable UIC estimates. RESULTS: Analyses were limited to 199 patients after excluding 11 who failed to return urine samples for measuring UIC and 2 outliers for UIC. Of the 199 patients, 36.2% had CME in 1 or both eyes. Although log CFT was inversely related to UIC based on findings from all eyes (P = .02), regression of log CFT on UIC separately for eyes with and without CME showed a strong inverse significant relationship for the former group (P < .001) and no significant relationship for the latter group (P = .66) as tested. For the eyes with CME, CFT ranged from a geometric mean of 267 µm for a median UIC of less than 100 µg/L to a geometric mean of 172 µm for a median UIC of 200 µg/L or greater. In contrast, we found no significant association between CME prevalence and UIC based on the entire sample as tested (odds ratio, 1.01 [95% CI, 0.38-2.67]; P = .99). CONCLUSIONS AND RELEVANCE: A higher UIC in nonsmoking adults with RP was significantly associated with less central foveal swelling in eyes with CME. Additional study is required to determine whether an iodine supplement can limit or reduce the extent of CME in patients with RP.

Blue-light reflectance imaging of macular pigment in infants and children.

PURPOSE: While the role of the macular pigment carotenoids in the prevention of age-related macular degeneration has been extensively studied in adults, comparatively little is known about the physiology and function of lutein and zeaxanthin in the developing eye. We therefore developed a protocol using a digital video fundus camera (RetCam) to measure macular pigment optical density (MPOD) and distributions in premature infants and in children. METHODS: We used blue light reflectance to image the macular pigment in premature babies at the time of retinopathy of prematurity (ROP) screening and in children aged under 7 years who were undergoing examinations under anesthesia for other reasons. We correlated the MPOD with skin carotenoid levels measured by resonance Raman spectroscopy, serum carotenoids measured by HPLC, and dietary carotenoid intake. RESULTS: We enrolled 51 infants and children ranging from preterm to age 7 years. MPOD correlated significantly with age (r = 0.36; P = 0.0142), with serum lutein + zeaxanthin (r = 0.44; P = 0.0049) and with skin carotenoid levels (r = 0.42; P = 0.0106), but not with dietary lutein + zeaxanthin intake (r = 0.13; P = 0.50). All premature infants had undetectable macular pigment, and most had unusually low serum and skin carotenoid concentrations. CONCLUSIONS: Our most remarkable finding is the undetectable MPOD in premature infants. This may be due in part to foveal immaturity, but the very low levels of serum and skin carotenoids suggest that these infants are carotenoid insufficient as a consequence of low dietary intake and/or severe oxidative stress. The potential value of carotenoid supplementation in the prevention of ROP and other disorders of prematurity should be a fruitful direction for further investigation.

Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage.

PURPOSE: Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage. METHODS: Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n-3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n-3 fatty acid intake. Retinas received 150-µm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage. RESULTS: In control animals, the fovea was less sensitive to blue-light-induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n-3 fatty acids showed greater sensitivity to damage than animals with adequate levels. CONCLUSIONS: After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light-induced damage, whereas adequate n-3 fatty acid levels reduced the damage in the parafovea.

Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.

BACKGROUND: The purpose of this study was to compare photodynamic therapy (PDT) against subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS: Patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If they declined PDT, then TTT was offered. RESULTS: We evaluated and followed 115 consecutive patients for an average of 1 year. The primary outcome measure was visual acuity, but the interventions were also compared on the basis of lesion size and angiographically determined lesion activity. Baseline comparisons between the 2 treatment groups showed significant differences in pretreatment visual acuity, lesion size, and lesion composition. Univariate analysis of outcomes demonstrated equivalence between the treatment groups in final lesion size, angiographic activity, and visual acuity. Multivariate analysis also demonstrated equivalence between the treatment groups in final visual acuity while controlling for age, pretreatment visual acuity, and lesion category. Predominantly classic lesions were associated with poorer visual outcomes. INTERPRETATION: The PDT and TTT groups were equivalent in terms of all outcome parameters evaluated.

Socioeconomic status and clinical features of patients undergoing photodynamic therapy or transpupillary thermotherapy for subfoveal choroidal neovascularization due to age-related macular degeneration.

BACKGROUND: The purpose of this study was to compare baseline clinical and socioeconomic features of patients undergoing self-funded photodynamic therapy (PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a diode laser for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). METHODS: Between July 2000 and August 2001, 115 patients with subfoveal choroidal neovascularization secondary to AMD were offered PDT as an initial intervention. If individuals believed that they could not afford or did not want PDT, then TTT was offered. In masked fashion, leakage pattern and lesion size were determined retrospectively from pretreatment angiograms. Baseline visual acuity was determined with autorefraction and subsequent Snellen testing. The mean income of each treatment group was estimated from the average sex-specific income for each subject's postal code, based on the 1996 Canadian census data. The average education level for each subject's postal code was also determined. RESULTS: The patients who were not willing to pay for PDT had significantly worse macular disease before treatment (larger lesions and poorer visual acuity) and a significantly lower mean income than the patients who were willing to pay for PDT. INTERPRETATION: The severity of exudative choroidal neovascularization appears to be associated with lower socioeconomic status.

Nutritional manipulation of primate retinas. IV. Effects of n--3 fatty acids, lutein, and zeaxanthin on S-cones and rods in the foveal region.

Lutein and zeaxanthin are xanthophylls selectively accumulated by primate retinas that may protect the macula from age-related macular degeneration. In this project, we manipulated n-3 fatty acids, lutein and/or zeaxanthin levels in the diet and studied their possible outcome on S-cone and rod cell density in the foveal region. Rhesus monkeys (7-16 year, n=17) were fed from birth xanthophyll-free semipurified diets with either adequate or low n-3 fatty acids. Five monkeys were supplemented with lutein and six with zeaxanthin for 6-24 months, while six remained xanthophyll-free until sacrifice. Retinas were embedded in methacrylate and serial 2 microm sections were cut along the vertical meridian. Rod nuclei, and immuno-labelled outer segments of S-cones and rods, were reconstructed and counted in an 8 microm strip. The density profiles were compared with data from control monkeys (n=7) fed a standard laboratory diet. S-cone density profiles were symmetrical along the vertical meridian and the densities decreased rapidly with retinal eccentricity. Rod densities were higher in the superior region than the inferior region in most of the control and experimental animals. Unlike the significant effects observed for retinal pigment epithelial cells of these same monkeys (Leung, I.Y-F., Sandstrom, M.M., Zucker, C.L., Neuringer, M., Snodderly, D.M., 2004. Nutritional manipulation of primate retinas. II. Effects of age, n-3 fatty acids, lutein, and zeaxanthin on retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 45, 3244-3256), neither xanthophyll supplementation nor low dietary n-3 fatty acids produced consistent effects on S-cone or rod density profiles of the experimental animals. However, monkeys low in n-3 fatty acids had increased variability of S-cone density in the fovea and low density of foveal rod outer segments. The high variability suggests that the photoreceptors of some animals were resistant to the nutritional manipulations, while others may have been affected. Thus, the photoreceptors appear less sensitive than the retinal pigment epithelium to these nutritional manipulations. However, it is possible that more consistent effects would emerge at a later age or after exposure to stressors such as high light levels.

Changes in foveal thickness and macular function after transpupillary thermotherapy for age-related macular degeneration.

PURPOSE: To evaluate the effect of transpupillary thermotherapy (TTT) on foveal thickness and macular function in eyes with choroidal neovascularization (CNV) associated with age-related macular degeneration. METHODS: Sixteen eyes with occult CNV and 6 eyes with classic CNV were treated with TTT. Optical coherence tomography and focal macular electroretinograms (FMERGs) elicited by a 15-degree stimulus were performed before, 3 months after TTT in 22 eyes and 6 months after TTT in 18 eyes. RESULTS: Before TTT, the fovea in 20 of the 22 eyes with CNV was significantly thicker than that of normal subjects. The foveal thickness was reduced after TTT in 11 of 14 eyes with occult CNV and remained unchanged in 2 eyes. One eye with occult CNV before TTT developed a classic CNV with significant macular edema and increased foveal thickness 3 months after TTT. The amplitudes of the FMERGs were reduced in all eyes before TTT. In eyes with occult CNV, the mean b-wave amplitude increased significantly after TTT (p = 0.0260 at 3 months, p = 0.0142 at 6 months). When the change of foveal thickness was less than 20% after TTT, all eyes with occult CNV had a 30% or more increase in the b-wave amplitude. In eyes with classic CNV, the mean amplitude of the a- and b-waves did not change significantly after TTT. CONCLUSIONS: TTT improves macular function in eyes with occult CNV associated with age-related macular degeneration more when the change of foveal thickness is slight.

Transpupillary thermotherapy in the management of juxtapapillary and parafoveal circumscribed choroidal hemangioma.

BACKGROUND: Circumscribed choroidal hemangioma (CCH) is a rare, vascular tumor that may be associated with formation of subretinal fluid, cystic retinal de-generation, and serous retinal detachment. Studies have suggested that proximity of this tumor to the fovea or optic nerve precludes the use of trans-pupillary thermotherapy (TTT) for treatment. We report our experience using TTT in managing patients with juxtapapillary and parafoveal CCH. METHODS: We reviewed the records of consecutive patients with CCH treated by TTT at Princess Margaret Hospital, Toronto, between November 1999 and March 2003. This resulted in 11 eyes of 11 patients with juxtapapillary or parafoveal tumors. Treatment was delivered via slit lamp using an 810 nm diode laser with 350 to 800 mW, a 3.0 mm spot, and duration range from 5 s to 90 s. Outcome measures were reduction in tumor thickness, resolution of serous fluid, tumor control, visual acuity, and complications of treatment. RESULTS: Mean age of patients was 47.6 years. Symptoms included blurred vision, metamorphopsia, light flashes, and floaters. Macular and optic disk edema, field defect, presence of subretinal fluid, and retinal detachment were noted. At presentation, Snellen visual acuity ranged from 20/70 to hand motions. Mean tumor base diameter was 6.0 mm and tumor thickness at baseline was 3.0 mm. Mean follow-up was 18.0 months. Post-TTT, mean tumor thickness was 2.8 mm. Macular and optic disk edema resolved in the majority of patients. Partial regression of the tumor was noted in 4 cases (36%) and good tumor control in 9 cases (82%). Visual acuity improved in 6 patients (55%). INTERPRETATION: TTT can be effective for treating juxtapapillary and para-foveal CCH. Proximity to the fovea and optic nerve may not be predictive of poor post-treatment visual acuity, although statistical analysis with a larger sample size would more clearly demonstrate a clear advantage.

Subthreshold transpupillary thermotherapy for subfoveal occult choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To describe the long term outcome of patients with subfoveal, occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) treated with subthreshold transpupillary thermotherapy. METHODS: 82 eyes of 82 consecutive patients with subfoveal occult CNV secondary to AMD were treated with subthreshold transpupillary thermotherapy. Best corrected visual acuity, fundus photography, fluorescein and indocyanine green angiography were performed. RESULTS: All patients have been followed for at least 24 months. At the final follow-up visit, 75.6% of patients had stable or improved visual acuity and 24.4% had worsened visual acuity. No overtreatment side effects were found. CONCLUSION: Subthreshold transpupillary thermotherapy seems effective in stabilizing visual acuity in patients affected by occult, subfoveal CNV even on a long-term basis.

Detachment of subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the entity of partial detachment and folding of subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). DESIGN: Interventional case reports. METHODS: Review of the features of CNV detachment in two patients with CNV due to ARMD by contact lens slit-lamp biomicroscopy, fluorescein angiography, optical coherence tomography, and three-dimensional confocal scanning laser indocyanine green (ICG) angiography. RESULTS: One patient out of approximately 300 (0.5%) ARMD patients treated by photodynamic therapy (PDT) developed partial CNV detachment and folding 6 weeks after the second PDT treatment. Another patient out of approximately 100 (1.0%) ARMD patients treated by transpupillary thermotherapy (TTT) developed partial CNV detachment and folding 6 weeks after the second TTT treatment. The CNVs were large (2,500 microm to 4,500 microm) and located between the retina and the retinal pigment epithelium. In each, these findings were clearly visualized by slit-lamp biomicroscopy. Fluorescein angiography demonstrated an associated retinal pigment epithelium tear in one patient. Optical coherence tomography showed distinctive features and confocal scanning laser ICG further delineated the detached folded CNV. The best-corrected visual acuity improved in one patient from 20/80 to 20/40 and in the other from counting fingers at 6 feet to 20/200 after the CNV detachment. CONCLUSIONS: Partial CNV detachment and folding represent a unique, not previously reported, and possibly favorable outcome of PDT and TTT. The low energy and selectivity of these treatments may explain this phenomenon.