Impact of loading phase, initial response and CFH genotype on the long-term outcome of treatment for neovascular age-related macular degeneration.

OBJECTIVE: Factors influencing the outcome of anti-VEGF treatment in neovascular AMD are still investigated. We analyzed the impact of a loading phase, the significance of an initial response for the long-term and the effect of the CFH polymorphism (p.His402Tyr) on treatment outcome. METHODS: Patients treated with ranibizumab for neovascular AMD were analyzed over a period of 24 months by assessing effects of loading phase, initial response and genotype of CFH rs1061170 (c.1204C>T, p.His402Tyr). RESULTS: 204 eyes were included. A change of +5.0 [-1;+11] letters and +1.5 [-5.5;+9.5] was observed with a median of 4 [3]; [7] and 10 [7]; [14] ranibizumab injections during 12 and 24 months, respectively. Loading phase was no significant predictor for treatment as VA outcome in eyes with and without loading phase was similar (p = 0.846 and p = 0.729) at 12 and 24 months. In contrast, initial response was a significant predictor for improving vision of 5 or more letters at 12 (p = 0.001; OR = 6.75) and 24 months (p = 0.01; OR = 4.66). Furthermore, the CT genotype at CFH rs1061170 was identified as a significant predictor for a favorable VA outcome at 12 and 24 months (OR = 6.75, p = 0.001 and OR = 4.66, p = 0.01). CONCLUSIONS: Our data suggest that clinical decisions regarding treatment may be guided by observing patients' initial response as well as their genotype of SNP rs1061170, while the criterion of loading phase may not bear the customary value.

Delayed appearance of high altitude retinal hemorrhages.

BACKGROUND: Retinal hemorrhages have been described as a component of high altitude retinopathy (HAR) in association with altitude illness. In this prospective high altitude study, we aimed to gain new insights into the pathophysiology of HAR and explored whether HAR could be a valid early indicator of altitude illness. METHODOLOGY/PRINCIPAL FINDINGS: 28 mountaineers were randomly assigned to two ascent profiles during a research expedition to Mt. Muztagh Ata (7546 m/24,751 ft). Digital fundus photographs were taken prior to expedition at 490 m (1,607 ft), during expedition at 4497 m (14,750 ft = base camp), 5533 m (18,148 ft), 6265 m (20,549 ft), 6865 m (22,517 ft) and 4.5 months thereafter at 490 m. Number, size and time of occurrence of hemorrhages were recorded. Oxygen saturation (SpO2) and hematocrit were also assessed. 79% of all climbers exhibited retinal hemorrhages during the expedition. Number and area of retinal bleeding increased moderately to medium altitudes (6265 m). Most retinal hemorrhages were detected after return to base camp from a high altitude. No post-expeditional ophthalmic sequelae were detected. Significant negative (SpO2 Beta: -0.4, p<0.001) and positive (hematocrit Beta: 0.2, p = 0.002, time at altitude Beta: 0.33, p = 0.003) correlations with hemorrhages were found. CONCLUSIONS/SIGNIFICANCE: When closely examined, a very large amount of climbers exhibit retinal hemorrhages during exposure to high altitudes. The incidence of retinal hemorrhages may be greater than previously appreciated as a definite time lag was observed between highest altitude reached and development of retinal bleeding. Retinal hemorrhages should not be considered warning signs of impending severe altitude illness due to their delayed appearance.

Rapid reduction of hard exudates in eyes with diabetic retinopathy after intravitreal triamcinolone: data from a randomized, placebo-controlled, clinical trial.

PURPOSE: To assess the effect of triamcinolone acetonide over 3 months on hard exudates in patients with diabetic macular oedema (DMO). METHODS: Thirty-two eyes of 16 patients with DMO and hard exudates were included in a randomized, placebo-controlled trial. Treated eyes received a single-dose (4 mg) intravitreal injection of triamcinolone acetonide. Control eyes received an injection of subconjunctival saline. RESULTS: The overall area of hard exudates decreased significantly between the baseline and 3-month visits in treated eyes, but not in control eyes. The mean change in level of hard exudates between the two visits was -0.75 arbitrary units (AU) (95% confidence interval [CI] -1.32 to -0.18) in the central plus inner circle (1500 microm) and -0.81 AU (95% CI -1.49 to -0.13) over the whole grid (3000 microm) in treated eyes, compared with 0.31 AU (95% CI -0.19 to 0.82) and 0.31 AU (95% CI -0.11 to 0.74), respectively, in control eyes (p < 0.001). Mean visual acuity improved by five letters in treated but not in control eyes (p = 0.01). CONCLUSIONS: Intravitreal triamcinolone reduces hard exudates in the short-term in eyes with DMO.

New insights into ocular blood flow at very high altitudes.

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

High incidence of optic disc swelling at very high altitudes.

OBJECTIVES: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

Quantitative OCT analysis of idiopathic perifoveal telangiectasia.

PURPOSE: To identify and quantitate specific changes in optical coherence tomography (OCT) images of patients with type 2 idiopathic perifoveal telangiectasia (IPT). METHODS: In a prospectively designed, observational, case-control study, 28 eyes of 14 consecutive patients with IPT were examined with OCT and compared with eyes of 14 unaffected control subjects. Light reflectivity profiles of raw scan data of OCT images were quantitatively analyzed for differences in distance between different retinal reflectivity layers and their respective reflectivities. Maculae were examined in four separate regions: (1) central fovea, (2) nasal perifovea, (3) temporal perifovea, and (4) outside the fovea. RESULTS: Retinal thinning, shortening of the photoreceptor outer segments and loss of reflectivity of the photoreceptor ellipsoid region were found in the central foveal region as well as the nasal and temporal perifoveal regions in eyes with IPT. In addition, increased reflectivity of the outer nuclear layer was found in a sharply demarcated area of the inferotemporal perifoveal region in all affected eyes. Retinal tissue located more than 2000 mum away from the foveola was indistinguishable from that in normal eyes. CONCLUSIONS: Quantitative OCT analysis shows unique and specific changes in the photoreceptors of the central macula in IPT which can be detected from first clinical presentation. These changes may be of use as an additional diagnostic tool. Correlation of the findings in the outer nuclear layer with histologic studies may help identify the nature of the reflectivity increase and define more clearly the type of damage sustained by the photoreceptors in this condition.

Differential optical densities of intraretinal spaces.

PURPOSE: To test the hypothesis that hyporeflective spaces in the neuroretina found on optical coherence tomography (OCT) examination have different optical reflectivities according to whether they are associated with exudation or degeneration. METHODS: Retrospective analysis of eyes with idiopathic perifoveal telangiectasia (IPT), diabetic macular edema (DME), idiopathic central serous chorioretinopathy (CSC), retinitis pigmentosa (RP), or cone dystrophy (CD) and eyes of healthy control subjects. OCT scans were performed. Raw scan data were exported and used to calculate light reflectivity profiles. Reflectivity data were acquired by projecting three rectangular boxes, each 50 pixels long and 5 pixels wide, into the intraretinal cystoid spaces, centrally onto unaffected peripheral RPE, and onto the prefoveolar vitreous. Light reflectivity in the retinal pigment epithelium (RPE), vitreous, and intraretinal spaces for the different retinal conditions and control subjects were compared. RESULTS: Reflectivities of the vitreous and the RPE were similar among the groups. Hyporeflective spaces in eyes with exudation (DME, RP, and CSC) had higher reflectivity compared with the mean reflectivity of the vitreous, whereas the cystoid spaces in the maculae of the eyes without exudation (CD and IPT) had a lower reflectivity than did the normal vitreous. CONCLUSIONS: Analysis of the light reflectivity profiles may be a tool to determine whether the density of hyporeflective spaces in the macula is greater or less than that of the vitreous, and may be a way to differentiate degenerative from exudative macular disease.

Is pseudophakia a risk factor for neovascular age-related macular degeneration?

PURPOSE: To examine the possible association between pseudophakia and neovascular age-related macular degeneration (AMD). METHODS: Reports of all patients undergoing fluorescein angiography in the authors' department over a 6-year period were retrospectively reviewed. Four hundred ninety-nine patients with recent onset of neovascular AMD in one eye and early age-related maculopathy (ARM) in the fellow eye were included in the study. Lens status (phakic or pseudophakic) in both eyes at the time of onset of neovascular AMD and the time between cataract surgeries (if performed) and onset of neovascular AMD were determined. RESULTS: There was no significant difference in lens status between eyes with neovascular AMD and fellow eyes with early ARM (115/499 [23.0%] vs. 112/499 [22.4%] pseudophakic; P = 0.88, odds ratio 1.035, 95% CI 0.770-1.391). Subgroup analysis revealed no difference between the groups with large drusen, small drusen, or pigmentary changes only (respectively, 20.3% vs. 19.6% pseudophakic, P = 0.92; 20.5% vs. 23.3% pseudophakic, P = 0.84; 33.3% vs. 31.7% pseudophakic, P = 1.0). Pseudophakic eyes with neovascular AMD had not been pseudophakic for a significantly longer period at the time of onset of neovascular AMD than their pseudophakic fellow eyes at the same time point (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, P = 0.27). CONCLUSIONS: The results do not support the hypothesis that pseudophakia is a major risk factor for the development of neovascular AMD.

Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial.

OBJECTIVE: To report 2-year safety and efficacy outcomes from a trial of intravitreal triamcinolone acetonide (TA) injections (4 mg) in eyes with diabetic macular edema and impaired vision that persisted or recurred after laser treatment. DESIGN: Prospective, double-masked, placebo-controlled, randomized clinical trial. PARTICIPANTS AND CONTROLS: Sixty-nine eyes of 43 patients were entered into the study, with 34 eyes randomized to receive active treatment and 35 placebo. Two-year data were available for 60 of 69 (87%) eyes of 35 of 41 (85%) patients; 9 eyes of 6 patients were lost to follow-up, of which 6 received a placebo and 3 received intravitreal TA. INTERVENTION: Triamcinolone acetonide (0.1 ml) was injected through the pars plana using a 27-gauge needle. Eyes randomized to placebo received a subconjunctival injection of saline. MAIN OUTCOME MEASURES: Improvement of best-corrected logarithm of the minimum angle of resolution visual acuity (VA) by > or =5 letters after 2 years and incidence of moderate or severe adverse events. RESULTS: Improvement of > or =5 letters' best-corrected VA was found in 19 of 34 (56%) eyes treated with intravitreal TA, compared with 9 of 35 (26%) eyes treated with the placebo (z(generalized estimating equation) = 2.73, P = 0.006). The mean improvement in VA was 5.7 letters (95% confidence interval, 1.4-9.9) more in the intravitreal TA-treated eyes than in those treated with the placebo. An increase of intraocular pressure (IOP) of > or =5 mmHg was observed in 23 of 34 (68%) treated versus 3 of 30 (10%) untreated eyes (P<0.0001). Glaucoma medication was required in 15 of 34 (44%) treated versus 1 of 30 (3%) untreated eyes (P = 0.0002). Cataract surgery was performed in 15 of 28 (54%) treated versus 0 of 21 (0%) untreated eyes (P<0.0001). Two eyes in the intravitreal TA-treated group required trabeculectomy. There was one case of infectious endophthalmitis in the treatment group. CONCLUSION: Intravitreal TA improves vision and reduces macular thickness in eyes with refractory diabetic macular edema. This beneficial effect persists for up to 2 years with repeated treatment. Progression of cataract and elevation of IOP commonly occur but appear manageable. Spontaneous improvement over years can still occur in eyes that are apparently severely affected by diabetic macular edema.

Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial.

OBJECTIVE: To determine whether an intravitreal injection of triamcinolone acetonide for persistent diabetic macular edema after adequate laser treatment improves visual acuity. DESIGN: Prospective, double-masked, placebo-controlled, randomized clinical trial. PARTICIPANTS AND CONTROLS: Sixty-nine eyes of 43 patients were entered into the study, with 34 eyes randomized to receive active treatment and 35 randomized to receive a placebo injection. Sixty-five of 69 eyes (94%) completed the 3-month study visit. INTERVENTION: Using a 27-gauge needle, 0.1 ml of triamcinolone acetonide was injected through the pars plana. The procedure was performed in a minor procedures area in the outpatient clinic under sterile conditions and using topical and subconjunctival anesthesia. Eyes randomized to placebo received a subconjunctival saline injection using the identical procedure for preparation. MAIN OUTCOME MEASURES: The main outcome measures were improvement of best-corrected logarithm of the minimum angle of resolution visual acuity by 5 or more letters and incidence of moderate or severe adverse events. RESULTS: Eighteen of 33 eyes (55%) treated with triamcinolone gained 5 or more letters of best-corrected visual acuity compared with 5 of 32 eyes (16%) treated with placebo (P = 0.002). Macular edema was reduced by 1 or more grades as determined by masked semiquantitative contact lens examination in 25 of 33 treated eyes (75%) versus 5 of 32 untreated eyes (16%; P<0.0001). Optical coherence tomography showed a mean reduction of central retinal thickness of 152 mum in the 21 treated eyes that were examined compared with a reduction of 36 mum in 20 placebo-treated eyes. Infectious endophthalmitis developed in 1 triamcinolone-treated eye that was treated adequately without loss of visual acuity. CONCLUSIONS: In the short term, intravitreal triamcinolone is an effective and relatively safe treatment for eyes with diabetic macular edema that have failed laser treatment. Although it will be essential to study longer-term outcomes, the use of intravitreal triamcinolone may be considered in 1 eye of patients who continue to lose vision from diabetic macular edema despite conventional management.

Ocular injuries caused by plastic bullet shotguns in Switzerland.

Five patients with blunt ocular trauma due to hard plastic shotguns used by police forces during riots presented to the Ophthalmology Department of University Hospital in Zurich, Switzerland, between December 2000 and May 2001. All five eyes suffered ocular concussion. Three of five eyes presented with severe damage to the anterior segment of the eye, two of these eyes showed combined involvement of the anterior and posterior segments. Two patients completely recovered their visual acuity in the injured eye, two reached a final visual acuity of 6/12 and in one case the injured eye was legally blinded. Three of the patients claimed to have been uninvolved bystanders at the riots. The theoretical probability of hitting the head/neck area or one of the two eyes for each shot fired at a person from different operational distances is calculated and ophthalmological and technical aspects of this special type of plastic bullet shotgun used in Switzerland are discussed.

Surgical treatment of diabetic retinopathy.

Several complications of advanced diabetic retinopathy can be treated surgically. Vitrectomy can clear media opacities, relieve traction on the retina, and makes adequate laser treatment of the retina possible. Removal of premacular vitreous may also improve diabetic macular edema. Instrumentation, understanding of the pathophysiology, surgical skills as well as supplementary pharmacotherapy have improved surgical results. Indications and timing for surgery have considerable changed in the past decades threshold for surgery has been continuously lowered, as vitrectomy became safer. The primary disease of the retinal microvasculature with capillary occlusion and retinal ischemia is still the limiting factor, responsible for disappointing functional results in anatomically successfully operated eyes.

Familial retinal arteriolar tortuosity: a review.

Familial retinal arteriolar tortuosity is a rare disorder with autosomal dominant inheritance. It is characterized by a pathognomic pattern of progressive, pronounced tortuosity of the arterioles of second and third order in the macular and peripapillary area developing during childhood or early adulthood. The disorder can be complicated by intra- or preretinal hemorrhages that occur spontaneously or during physical exertion. These hemorrhages can be asymptomatic if they do not involve the fovea. Clearing of the hemorrhages without treatment and recovery of full visual acuity is the rule, even if the central macula is involved. In most cases, no other vascular malformations or associated systemic diseases have been found. In some cases, retinal hemorrhages may precede the development of the tortuosity or the tortuosity may remain subtle, even if the patients suffer from recurrent hemorrhages. The ophthalmologist should be aware of familial retinal arteriolar tortuosity as a possible cause for retinal hemorrhages.

Ocular complication of PhotoDerm VL therapy for facial port-wine stain.

BACKGROUND: A case of focal damage to the iris with distortion of the pupil secondary to PhotoDerm therapy in a 2-year-old boy is reported. OBJECTIVE: To study ocular complication of photoDerm VL therapy for facial port-wine stain. METHODS. : Observatory case report. RESULTS: PhotoDerm VL therapy may damage ocular tissues. CONCLUSION: Appropriate protection during the procedure is essential.