Potential Effects of Hormone Therapy in Type 2 Idiopathic Macular Telangiectasia.

PURPOSE: To investigate the influence of hormone therapy with tamoxifen or estrogens on morphological changes in macular telangiectasia (MacTel) type 2 patients as revealed clinically in multiple imaging modalities. METHODS: Patients with a history of tamoxifen or estrogen use were selected from the cohort of the MacTel Study. A race-, age- and best-corrected visual acuity-matched group of MacTel participants not under hormone therapy served as the comparison group. The frequencies of typical features of the MacTel phenotype apparent in color fundus, red-free, fluorescein angiographic and optical coherence tomographic images were graded and analyzed statistically. RESULTS: Thirty-nine MacTel patients were included in the analyses, of whom 13 were receiving tamoxifen, 13 estrogens and 13 patients no hormone treatment. Patients treated with estrogens showed significantly fewer breaks in the ellipsoid zone on optical coherence tomography (7 eyes, 29.1%, vs. tamoxifen: 14 eyes, 53.8%, and vs. controls: 14 eyes, 53.8%, p = 0.04 in both analyses, Fisher exact test). Retinal crystalline deposits were significantly more frequent in patients receiving estrogens (12 eyes, 16.2%, vs. 2 eyes, 2.7%, p = 0.003, Fisher exact test). No significant between-group differences were apparent with regard to other features of the phenotype (extent of retinal low reflective spaces, late hyperfluorescence on fluorescein angiography or retinal thickness). CONCLUSIONS: Tamoxifen treatment does not seem to accentuate structural changes in patients with MacTel type 2. Treatment with estrogens may exhibit a neuroprotective effect as suggested by the decreased frequency of ellipsoid zone breaks in corresponding patients, although corroborative studies are warranted to confirm these exploratory data.

Oral Lutein Supplementation Enhances Macular Pigment Density and Contrast Sensitivity but Not in Combination With Polyunsaturated Fatty Acids.

PURPOSE: It has been shown that lutein and zeaxanthin accumulate in the macula where they enhance contrast sensitivity and may reduce the risk of progression to advanced age-related macular degeneration (AMD). Furthermore, omega-3 long-chain polyunsaturated fatty acids (PUFA) might further reduce this risk. However, controversy exists regarding whether PUFA may reduce the bioavailability of lutein. METHODS: This was a prospective 12-month, randomized, open label study evaluating the effect of supplementation with lutein, other antioxidants, and minerals on contrast sensitivity (CS) and macular pigment optical density (MPOD) in patients with age-related maculopathy. A total of 79 patients were randomized to either lutein (10 mg) and antioxidant supplement or lutein and antioxidant supplement in combination with PUFA. Patients received supplementation for a period of 6 months and were followed for a total of 12 months. RESULTS: Serum lutein and zeaxanthin increased significantly by the first follow-up visit at 1 month, and remained elevated throughout the intervention period of 6 months in the lutein-only group but not in the lutein+PUFA group. Macular pigment optical density and CS increased significantly in the lutein-only group (P < 0.005) but not in the lutein+PUFA group (P = 0.059) compared to baseline. Best-corrected visual acuity remained unchanged during the entire study period in both groups. CONCLUSIONS: Addition of PUFA may reduce the bioavailability of lutein and therefore lessen the beneficial effect on macular pigment and CS. This needs to be considered when prescribing lutein supplements to patients with low lutein levels. (ClinicalTrials.gov number, NCT00563979.).

Vitreoretinal interface changes in geographic atrophy.

PURPOSE: Geographic atrophy (GA) is the end-stage manifestation of atrophic age-related macular degeneration (AMD). The disease progresses slowly over time, eventually causing loss of central vision. Its cause and pathomechanism are not fully known. Previous studies have suggested that vitreoretinal traction (VRT) may contribute to the progression of neovascular AMD. The aim of this study was to examine whether an association between changes at the vitreoretinal interface (VRI), in particular traction (VRT), and the characteristics and progression of GA in eyes with dry AMD can be established. DESIGN: Clinic-based prospective cohort study. PARTICIPANTS: A total of 97 patients (age range, 61-90 years; mean, 78.4 years) with GA secondary to dry AMD were enrolled. Patients exhibiting neovascular signs on fluorescein angiography in either eye were excluded. METHODS: The VRI changes were examined using spectral-domain optical coherence tomography (SD-OCT). Characteristics of GA were examined using fundus autofluorescence (FAF) imaging. All imaging was performed using a Spectralis SLO+OCT device (Heidelberg Engineering, Heidelberg, Germany); GA area was measured using the Region Finder (Heidelberg Engineering) software native to the Spectralis platform. MAIN OUTCOME MEASURES: Area and increase in area of GA. RESULTS: A total of 97 eyes were examined. Vitreoretinal traction was found in 39 eyes (40%). The GA area at baseline was 6.65±5.64 mm(2) in eyes with VRT and 5.73±4.72 mm(2) in eyes with no VRT. The annual rate of progression of GA area progression was 2.99±0.66 mm(2) in eyes with VRT and 1.45±0.67mm(2) in eyes without VRT. Differences between groups in both parameters were statistically significant (n = 97 total number of eyes; P<0.001). Multiple regression analysis confirmed this finding (B = 0.714, P<0.001; F3,93 = 72.542, P<0.001; adjusted R(2) = 0.691) CONCLUSIONS: Our results indicate an association between VRT and an increased rate of progression of GA area in dry AMD. Monitoring VRT may contribute to an improved estimate of the prospective time of visual loss and to a better timing of emerging therapies in dry AMD.

Detection of Chlamydia and complement factors in neovascular membranes of patients with age-related macular degeneration.

PURPOSE: To investigate whether Chlamydia pneumoniae and complement factors were present in surgically removed choroidal neovascular membranes (CNV) of patients with age-related macular degeneration (AMD). METHODS: Paraffin sections of 26 CNV were stained for C. pneumoniae or the complement factors H (CFH) and C5, whereas macrophages were identified by positive CD68 staining. Clinical characteristics have been correlated to the immunohistochemical findings. RESULTS: C. pneumoniae was found in 68% of the investigated membranes, and 88% of these membranes were also positive for CD68. Staining for CFH and C5 gave a positive reaction in 68 and 41% of the membranes, respectively. Patients with C5-positive membranes had significantly larger CNV mean area and were younger than patients with CFH-positive membranes at the operation time point. CONCLUSIONS: Correlations between clinical symptoms and complement factor C5 could be shown. The results strengthen the hypothesis of an involvement of the complement system in AMD.

Three-year results of visual outcome with disease activity-guided ranibizumab algorithm for the treatment of exudative age-related macular degeneration.

PURPOSE: To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. METHODS: A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. RESULTS: Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. CONCLUSIONS: Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.

The IS/OS junction layer in the natural history of type 2 idiopathic macular telangiectasia.

PURPOSE: To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS: Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed. RESULTS: thirty-nine eyes of 23 patients (mean age: 62.3 ± 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006). CONCLUSIONS: Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel.

"En face" OCT imaging of the IS/OS junction line in type 2 idiopathic macular telangiectasia.

PURPOSE: We investigated abnormalities of the photoreceptor inner/outer segment (IS/OS) junction layer viewed "en face" and their functional correlates in type 2 idiopathic macular telangiectasia (type 2 MacTel). METHODS: Segmentation and "en face" imaging of the IS/OS lines in spectral domain optical coherence tomographic (SD-OCT) volumes were performed manually. Mesopic retinal sensitivity thresholds were determined using a Nidek MP1 microperimeter. "En face" SD-OCT images and microperimetric data were superimposed over images of the fundus. Retinal structure and characteristics of type 2 MacTel were analyzed, and associations of structural changes with function were investigated. RESULTS: We examined 49 eyes of 28 patients (mean age 62.6 ± 9.4 years). Total IS/OS break area ranged from 0.04 to 2.23 mm² (mean 0.63 mm², SD 0.53 mm²) and 0.03 to 1.49 mm² (mean 0.49 mm², SD 0.42 mm²) in right and left eyes, respectively. A correlation between fellow eyes was present (Spearman correlation ρ = 0.770, P < 0.01). An assessment of the repeatability of IS/OS lesion area measurements (n = 19 eyes) revealed an intra-class correlation coefficient of 0.99 (95% confidence interval [CI] of 0.975-0.996). Retinal areas corresponding to an IS/OS break showed a mean retinal sensitivity of 8.3 ± 5.8 and 8.7 ± 5.7 decibels (dB) in right and left eyes, respectively. Mean sensitivity over retinal areas outside the lesion was significantly higher, 17.0 ± 3.3 and 16.7 ± 3.6 dB in right and left eyes, respectively (paired t-test, P < 0.01). Mean aggregate retinal sensitivity loss was 33.5 ± 30.4 dB (n = 40), correlating well with IS/OS lesion area (Pearson correlation coefficient = 0.848, P < 0.01). CONCLUSIONS: "En face" OCT imaging of the IS/OS junction layer provides a functionally relevant method for assessing disease severity in type 2 MacTel.

Association of macular pigment density with plasma ω-3 fatty acids: the PIMAVOSA study.

PURPOSE: To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs). METHODS: The PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination. RESULTS: MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14). CONCLUSIONS: In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.

Intraocular pressure changes following 20G pars-plana vitrectomy.

PURPOSE: To observe the excursions of short-term intraocular pressure (IOP) after 20-G pars-plana vitrectomy (ppV). MATERIAL AND METHODS: In a prospective study, 851 patients (age: mean 63 ± 15 years) underwent unilateral ppV for various vitreoretinal diseases using different endotamponades [Balanced Salt Solution (BSS) 33.1%, Air 7.2%, SF(6) 33.6%, silicon oil 5000 cst 26.1%]. Intraocular pressure was measured in all patients before and at 3, 6, 24 and 48 hr after surgery. Survival analysis was performed to determine the cumulative hazard of IOP changes depending on endotamponade and time point after ppV (Log-Rang - Mantel Cox; p < 0.0001). RESULTS: At baseline, IOP ranged from 0 to 50 mmHg (mean IOP: 15.3 ± 5.3 mmHg). Mean IOP after surgery revealed a slight elevation (3 hr: 16.5 ± 11.0 mmHg; 6 hr 16.9 ± 9.8 mmHg; 24 hr 19.7 ± 8.0 mmHg; 48 hr 17.3 ± 6.2 mmHg; range: 0-64 mmHg). Silicon oil filling revealed highest mean values at already 3 hr after surgery (21.8 mmHg). Also, BSS filling showed a peak after 3 hr; however, mean values were lower. Equivalent high IOP values as for silicon oil tamponade were found for gas filling; however, maximal peak was reached after 24 hr but not after 3 hr post-treatment. The cumulative hazard in all patients to reach IOP ≥ 30 mmHg after 24 hr was 23.9%; (IOP ≥ 40 mmHg = 8.2%). Herein, oil filling revealed highest risk at all time points after surgery. The risk of suffering from IOP < 5 mmHg lasting longer than 6 hr was only 1.2% after 20 G vitrectomy. CONCLUSION: Intraocular pressure measurements after ppV are important to prevent unintentional high IOP, especially within the early phase (3 hr post-treatment) in eyes with silicon oil filling. Gas filling leads to prolonged IOP increase (24 hr post-treatment). Long-lasting hypotony (≥ 6 hr) is very rare after 20G vitrectomy.

Blue-light versus green-light autofluorescence: lesion size of areas of geographic atrophy.

PURPOSE: Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF. METHODS: Patients older than 50 years with central areas of geographic atrophy (GA) secondary to ARMD were enrolled. Images were recorded with a modified confocal scanning laser ophthalmoscope (cSLO). Image quality and patterns were analyzed. The quantification of the GA was performed with customized image-analysis software. RESULTS: In total, 95 eyes were included. The borders of the central atrophic patches and the boundaries of the preserved foveal island were better identified in 514-nm images. In both excitation wavelengths the signal-to-noise ratio was sufficient for the identification of the FAF pattern. Significant differences were observed in the size of the GA areas detected in the 488- and 514-nm wavelength images (4.29 ± 3.76 mm(2) vs. 3.80 ± 3.68 mm(2); P < 0.001). CONCLUSIONS: The green-light FAF images (514 nm) are superior for the accurate analysis of small, central, pathologic changes, and for the determination of the central GA lesion size. Using only blue-light FAF could lead to an overinterpretation of the size of atrophic patches and the center involvement, because it suggests the presence of atrophy in the fovea.

Retinal crystals in type 2 idiopathic macular telangiectasia.

PURPOSE: To characterize the phenotype and investigate the associations of intraretinal crystalline deposits in a large cohort with type 2 idiopathic macular telangiectasia (MacTel). DESIGN: Case-control study. PARTICIPANTS: Patients with and without retinal crystals from the Macular Telangiectasia Project, an international multicenter prospective study of type 2 MacTel. METHODS: Grading of stereoscopic 30-degree color fundus (CF), confocal blue light reflectance (CBR), red-free (RF), and infrared (IR) images was performed according to the MacTel Natural History Study protocol and staged using the classification system devised by Gass and Blodi. Spectral domain-optical coherence tomography (SD-OCT) and adaptive optics imaging were used for a finer analysis of the phenotype. Associations between crystals and other characteristics of the disease, as well as potential risk factors, were investigated. MAIN OUTCOME MEASURES: Presence of crystals, fundus signs of MacTel, clinical characteristics, and presence of potential risk factors of MacTel. RESULTS: Of 443 probands enrolled in the MacTel study, 203 (46%) had crystalline deposits present; 60% of the cases were bilateral at baseline. Eyes with crystals had a mean letter score of 70.7 (standard deviation [SD] = 15.9), whereas those without crystals had a mean letter score of 66.5 (SD = 15.5, P < 0.001). Crystals were present at all stages of the disease and showed high reflectivity within a wide wavelength range. They were located at the anterior surface of the nerve fiber layer, arranged along the nerve fibers, within an annular area centered on the fovea. Significant associations of crystalline deposits were found with a loss of retinal transparency, macular pigment optical density (MPOD) loss, fluorescein leakage, retinal thickness, and a break in the inner segment/outer segment junction line. Associations with environmental risk factors were not found. CONCLUSIONS: Intraretinal crystals are a frequent phenomenon associated with type 2 MacTel. They may appear at all stages and aid in the early diagnosis of the disease. Their morphology further implicates Müller cells in the pathogenesis of the disease. Insight into their physical and chemical properties may provide clues to the metabolic pathways involved in the pathogenesis of the disease. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Caspase-3-independent photoreceptor degeneration by N-methyl-N-nitrosourea (MNU) induces morphological and functional changes in the mouse retina.

BACKGROUND: Retinal degeneration is followed by significant changes in the structure and function of photoreceptors in humans and several genetic animal models. However, it is not clear whether similar changes occur when the degeneration is induced pharmacologically. Therefore, our aim was to investigate the influence of retinotoxic N-methyl-N-nitrosourea (MNU) on the function, morphology and underlying molecular pathways of programmed cell death. METHODS: C57/BL6 mice were injected with different doses of MNU, and function was determined by analysing optokinetic reflex measurements and cued water maze results at several time points post-injection. Morphometric measurements were also taken from H&E-stained paraffin eye sections. TUNEL-positive cells and caspase-3 and -6 were detected by immunohistochemistry. To assess the molecular changes leading to cell death, qRT-PCR from neurosensory retina mRNA was performed. RESULTS: The application of MNU led to an instant decrease in function and a delayed decrease in the thickness of the retinal outer nuclear layer. These responses were observed in the absence of any structural changes in the retinal pigment epithelium. The degeneration of the photoreceptor cell layer was highest with 60 mg/kg MNU. The assessment of TUNEL-positive cells visualised cell death after treatment, but no detectable caspase-3 activity was observed concomitant with these changes. qRT-PCR revealed the possible involvement of the inflammatory mediator caspase-1 and endoplasmic reticulum stress-mediated apoptosis by caspase-12. CONCLUSION: MNU leads to the dose-dependent degeneration of photoreceptor cells in mice by caspase-3-independent pathways and is, therefore, a suitable model to study retinal degeneration in an animal model.

Macular pigment density at the site of altered fundus autofluorescence.

BACKGROUND: The purpose of our study was to determine whether abnormalities of increased or decreased fundus autofluorescence (FAF) are associated with local changes in macular pigment (MP) optical density in patients with age-related maculopathy (ARM) and macular degeneration (ARMD). METHODS: FAF imaging and MP measurement was performed through dilated pupils using a modified confocal scanning laser ophthalmoscope (HRA, Heidelberg Engineering, Germany) according to a standard protocol. Two-wavelength autofluorescence method was employed for determination of local macular pigment optical density (LMPOD). Image analysis and measurement of LMPOD at the area of altered FAF was performed using Heidelberg Eye Explorer Software. Mean values of LMPOD at the site of FAF abnormality were compared to an adjacent location with normal background FAF of the same image. RESULTS: Sixty-three eyes of 63 patients (28 male, 35 female, mean age 75.8 ± 8.8 years) were included in this analysis. Group 1 comprised 31 cases with focal increased FAF. Mean LMPOD in the area of increased FAF was 0.073 ± 0.083 compared to 0.075 ± 0.074 in the adjacent area of normal FAF. Group 2 comprised 32 cases of focal decreased FAF. Mean LMPOD in the area of decreased FAF was -0.004 ± 0.088 compared 0.053 ± 0.075 in the adjacent area of normal FAF. The site of increased FAF showed no significant difference in LMPOD (p = 0.927) compared to adjacent areas of normal FAF, while areas of decreased FAF revealed significantly lower LMPOD (p = 0.001) compared to adjacent areas of normal FAF. CONCLUSIONS: Focal increases of FAF due to ARM or ARMD did not lead to change in LMPOD. Presumably, retinal layers containing MP are unaffected by these processes. For lesions exhibiting focal decreased FAF, a reduction of LMPOD cannot be excluded. Further studies are needed to investigate MP in the course of disease.

Effects of combination therapy with verteporfin photodynamic therapy and ranibizumab in patients with age-related macular degeneration.

PURPOSE: This open-label, prospective, small-scale study investigated the benefits of same-day verteporfin and intravitreal ranibizumab in patients with predominantly classic, minimally classic or occult subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: Patients received verteporfin at baseline and at month 3, if leakage persisted. Ranibizumab (0.5 mg) was given at baseline and months 1, 2 and 3, and thereafter at monthly intervals if required. Same-day ranibizumab was given ≥ 1 hr after verteporfin. RESULTS: Fifteen patients [11 male, four female; mean age 75.5 years (range 54-94 years)] were treated. At day 360, mean visual acuity (VA) had improved by 10.9 letters. An increase of ≥ 15 and ≥ 30 letters (i.e. ≥ 3 and ≥ 6 lines) was observed in seven (47%) patients and one patient (7%), respectively. Mean central retinal thickness (CRT) decreased by 85 µm. At days 7, 14 and 30, CNV perfusion was absent in 14/15 patients. Mean lesion area had reduced from baseline by 23.1% at day 120, 25.5% at day 180 and 23.6% at day 360. There were no visual safety concerns and intraocular pressures remained normal. Only two serious adverse events were recorded over the 12-month period, and neither was considered to be related to treatment. CONCLUSION: Same-day verteporfin plus ranibizumab improved VA, reduced CRT, prevented CNV perfusion and reduced lesion area safely over 12 months. Further investigation is warranted to confirm whether this combination improves long-term vision and reduces the need for retreatment.

Predictors of short-term visual outcome after anti-VEGF therapy of macular edema due to central retinal vein occlusion.

PURPOSE: The purpose of this study was to analyze predictive factors for best-corrected visual acuity (BCVA) after anti-VEGF treatment in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS: This prospective study enrolled treatment-naive patients with ME secondary to CRVO. BCVA, ophthalmoscopy, fundus photography, and spectral domain optical coherence tomography (SD-OCT) imaging were performed. SD-OCT was analyzed for integrity of the external limiting membrane (ELM), photoreceptor inner segments (IS), and outer segments (OS). Patients were treated with intravitreal bevacizumab (1.25 mg) or ranibizumab (0.5 mg). BCVA outcome was analyzed 4 weeks after the first injection. RESULTS: Sixty-two eyes of 62 patients (39 men, 23 women; mean age: 67 ±16 years) were included. In 55%, the ELM was intact. These eyes also showed intact photoreceptor IS/OS in horizontal and vertical single scans. Disturbed ELM was seen in 45% and was accompanied by focal disintegration of IS/OS. Four weeks after injection, 58% showed clinically relevant increases of BCVA (≥5 letters). Mean BCVA ranged from 20 to 86 letters. The mean BCVA increase was 18 ± 12 letters in eyes with intact ELM compared with 4 ± 10 letters with disturbed ELM (P < 0.001). CONCLUSIONS: Depending on the integrity of the outer retinal layers, the authors observed rapid and clinically relevant improvement in BCVA after the first anti-VEGF injection. In the development of an optimal treatment regime, the indication for treatment and re-treatment should be based on functional and morphologic findings, such as the deterioration of outer retinal layers. Intact ELM in SD-OCT imaging is associated with better visual outcomes after intravitreal anti-VEGF treatment in patients with ME secondary to CRVO.

Simple and objective method for routine detection of the macular pigment xanthophyll.

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

Complement Factor P in choroidal neovascular membranes of patients with age-related macular degeneration.

PURPOSE: To evaluate whether complement Factor P (properdin) was present in surgically removed choroidal neovascular membranes of patients with age-related macular degeneration (AMD) and to investigate whether associated pre- and postoperative clinical characteristics can be correlated. METHODS: The study population consisted of 26 AMD patients (26 eyes) with the exclusion criterion of prior treatment of the choroidal neovascular membranes. Factor P was detected immunocytochemically on paraffin sections (7 microm) by a polyclonal rabbit antihuman antibody. RESULTS: Eleven of 22 assessable membranes showed a positive reaction for Factor P. The average percentage of Factor P-positive cells per membrane ranged from 0.65% to 4.09%. The duration of visual loss was significantly longer (8.6 +/- 2.7 vs. 3.9 +/- 0.8 months), and the size of postoperative measured area of atrophic retinal pigment epithelium was larger (27.6 +/- 7.6 vs. 15.0 +/- 6.9 mm2) in patients with Factor P-positive membranes compared with Factor P-negative ones. CONCLUSION: Factor P was expressed in 50% of choroidal neovascular membranes of patients with AMD. The group with Factor P-positive membranes differed significantly from the Factor P-negative group in key clinical outcomes. Additional studies need to investigate the role of Factor P in the development of AMD for potential therapeutic intervention.

Decreased visual function after patchy loss of retinal pigment epithelium induced by low-dose sodium iodate.

PURPOSE: To correlate damage to the retinal pigment epithelium (RPE) with decreased visual function after the systemic administration of sodium iodate (NaIO(3)). METHODS: Damage was produced in mice by injection of 15, 25, or 35 mg/kg NaIO(3). Visual function was assessed with the cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different times after injection. Autofluorescence in whole eye flatmounts was quantified, and hematoxylin and eosin staining of paraffin sections was performed to assess changes in the outer retina. RESULTS: After 15 mg/kg NaIO(3), cued WM test results were normal, whereas OKR measurements were significantly decreased at all times. Focal RPE loss began on day 21, but no significant damage to the outer nuclear layer was observed. After 25 mg/kg NaIO(3), the cued WM test was transitionally reduced and the OKR measurement again decreased at all times. Large areas of RPE loss occurred on day 14 with a reduced outer nuclear layer on the same day. With 35 mg/kg NaIO(3), the cued WM test was reduced beginning on day 14 with complete obliteration of the OKR beginning on day 3, large areas of RPE loss on the same day, and a reduced outer nuclear layer on day 7. CONCLUSIONS: Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.

Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration.

PURPOSE: To demonstrate not only prevention of vision loss but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). DESIGN: Interventional case series. SETTING: Institutional. STUDY POPULATION: One hundred and thirty-eight eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab (Lucentis; Novartis, Basel, Switzerland). Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. OBSERVATION PROCEDURES: After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia, and loss of BCVA > 5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. MAIN OUTCOME MEASURES: Compared with baseline: proportion of eyes gaining > or = 15 letters, proportion of eyes losing or gaining < 15 letters, change in CRT. RESULTS: After 24 months, 30% of eyes gained > or = 15 letters. After 24 months, 55% of eyes lost or gained < 15 letters. Mean CRT of 386 +/- 145 microm at baseline was significantly reduced to 211 +/- 39 microm after 24 months (P = .036). Mean injection number per patient was 5.6 +/- 2.9 and 4.3 +/- 3.8 from baseline to month 12 and month 12 to 24, respectively. CONCLUSION: Intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BVCA and reducing CRT. This beneficial outcome was achieved with a low-rate of mild ocular adverse effects among our patients.

Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments.

PURPOSE: To compare central retinal thickness (CRT) measurements in healthy eyes by different commercially available OCT instruments and to compare the intersession reproducibility of such measurements. METHODS: Six different OCT instruments (Stratus OCT [Carl Zeiss Meditec, Inc. Dublin, CA], SOCT Copernicus [Reichert/Optopol Technology, Inc., Depew, NY], Spectral OCT/SLO [Opko/OTI, Inc., Miami, FL], RTVue-100 [Optovue Corp., Fremont, CA], Spectralis HRA+OCT [Heidelberg Engineering, Inc., Heidelberg, Germany], and Cirrus HD-OCT [Carl Zeiss Meditec, Inc.]) were used to assess CRT in both eyes of healthy subjects. Measurements were performed in two different sessions on the same day with each of the systems. From these measurements, the mean CRT was calculated. For the assessment of the intersession reproducibility of the instruments, we calculated the coefficient of the variation of test-retest variation. RESULTS: Twenty healthy subjects were included in the study. Compared with the Stratus OCT all spectral OCT instruments showed significantly higher CRTs. The Spectralis HRA+OCT and Cirrus HD-OCT showed similar CRT values but significantly higher values than did all other instruments. The coefficients of variation for repeated measurements was 3.33% for the Stratus OCT, 0.46% for the Spectralis HRA+OCT, 3.09% for the Cirrus HD-OCT, 2.23% for the OCT/SLO, 2.77% for the RTVue-100 OCT, and for the SOCT 3.5%, respectively. discussion. The six OCT systems provided different results for CRT. The measurements with the Stratus OCT showed the lowest thicknesses, whereas those with the Cirrus HD-OCT and Spectralis HRA+OCT yielded the highest ones. These discrepancies can be explained by the differences in the retinal segmentation algorithms used by the various OCT systems. Whereas the Spectralis HRA+OCT and Cirrus HD-OCT include the RPE layer in the retinal segmentation, the other instruments do not. The data imply that the different OCT systems cannot be used interchangeably for the measurement of macular thickness.