[Combination of Intravitreal rTPA, gas and ranibizumab for extensive subfoveal haemorrhages secondary to neovascular age-related macular degeneration]. / Kombinierte intravitreale Injektion von rTPA, Gas und Ranibizumab zur Behandlung grossflächiger subfovealer Blutungen bei neovaskulärer altersbedingter Makuladegeneration.

BACKGROUND: The aim of this study was to evaluate the clinical outcomes of the combination therapy with intravitreal recombinant tissue plasminogen activator (rTPA), gas and lucentis for patients with extensive subfoveal haemorrhages secondary to neovascular age-related macular degeneration (AMD). METHODS: In this retrospective clinical study 10 eyes with extensive subfoveal haemorrhages secondary to neovascular AMD were included and treated with intravitreal rTPA (0.05 mL; 0.025 mg/0.1 mL in 0.9% NaCl), 100% sulphur hexafluoride (SF(6)) gas (0.5 mL) and lucentis (0.05 mL, 10 mg/mL) within two weeks after the onset of the subretinal haemorrhage. Retreatments with lucentis were performed at 4-week intervals if there were persistent submacular haemorrhages or signs of active choroideal neovascularisation (CNV). The treatment effect was evaluated using best-corrected visual acuity (VA, Snellen), complete ophthalmic examination, fluorescein angiography (FLA) and optical coherence tomography (OCT). RESULTS: Mean observation period was 6.4 A+/- 3.7 months (range: 3 - 13 months). With regard to VA, in 7 eyes there was an increase in VA (> or = 1 Snellen lines), in 1 eye a stabilisation and in 2 eyes a decrease in VA (> or = 1 Snellen lines). At the end of follow-up time, with regard to VA no significant difference was observed compared to baseline (p = 0.41). In 1 patient an intra-operative transient central arterial occlusion and in another patient a corneal erosion and an increase of intraocular pressure up to 27 mmHg were observed after initial combination treatment. On average there were 1.9 A+/- 1.3 retreatments indicated after initial treatment. CONCLUSION: The combination of rTPA, gas and lucentis is a valuable therapy for extensive subfoveal haemorrhages secondary to neovascular AMD resulting in stabilisation of both VA and morphologic parameters.

[The role of Stratus OCT in anti-VEGF therapy. Qualitative and quantitative assessment of neovascular AMD]. / Die Rolle des Stratus-OCT bei der Anti-VEGF-Therapie : Qualitative und quantitative Beurteilung bei neovaskulärer AMD.

BACKGROUND: The evaluation of OCT3 during anti-VEGF therapy. METHODS: A total of 29 patients with choroidal neovascularization secondary to AMD received 3 intravitreal injections of ranibizumab. OCT examination and visual acuity testing (ETDRS) were performed before therapy onset, after 1 week and after 1, 2 and 3 months. RESULTS: The central retinal thickness (CRT) was assessed correctly by OCT in 128 out of 145 measurements. There was a distinct (84%) but not significant correlation between decrease in central retinal thickness and increase in visual acuity. Incorrect retinal layer segmentation and inadequate CRT measurements were a significant technical limitation. CONCLUSION: During anti-VEGF therapy, OCT allows documentation and quantification of morphologic retinal changes and in most cases also for an estimation of functional improvement.

Quantification of optic nerve blood flow changes using magnetic resonance imaging.

PURPOSE: To evaluate the possibilities of magnetic resonance imaging (MRI) for quantification of pharmacologically induced changes in optic nerve microcirculation. METHOD: T2-weighted MRI sequences were used to image the eye, optic nerve, and frontal cortex in rats. Two sets of control images before and one set during Gd (DTPA) infusion were recorded. Blood flow values for two regions of the optic nerve (an anterior part, including the optic nerve head, and a more posterior part) and the frontal cortex were calculated by image analysis from the change in signal intensity, as already reported for cerebral blood flow. For each rat, a control experiment before drug administration and a second experiment 30 minutes after subcutaneous injection of either placebo (n = 7), timolol (n = 7), or SDZ GLC-756, a dopamine D-1 antagonist and D-2 agonist (n = 7), were carried out in a double-blind fashion. RESULTS: Mean basal blood flow values were found between 29.4 and 45.6 ml/100 g per minute in the anterior part of the optic nerve, 38.3 and 42.9 ml/100 g per minute in the posterior part of the optic nerve, and 68.0 and 75.0 ml/100 g per minute in the frontal cortex. Placebo and timolol did not cause significant changes. SDZ GLC-756 significantly increased blood flow by 238% +/- 65% in the anterior part and by 87% +/- 40% in the posterior part of the optic nerve. CONCLUSIONS: These results suggest that MRI provides quantification of optic nerve blood flow and that dopaminergic substances increase optic nerve blood flow.

Potential role of nitric oxide and endothelin in the pathogenesis of glaucoma.

Glaucoma is an optic nerve head neuropathy in which retinal ganglion cells are lost. A clear association exists between glaucoma and different risk factors, such as high intraocular pressure (IOP) or blood-flow dysregulation. Nitric oxide (NO) and endothelin, two recently identified cellular mediators, appear to be involved in the regulation of IOP as well as in the modulation of ocular blood flow. To some extent, NO is also involved in apoptosis, a mechanism of cell death that can lead to retinal ganglion cell loss in glaucoma. This article provides a short and simplified overview of the biochemistry of NO and endothelin and highlights the potential role of these two mediators in certain important aspects related to the pathogenesis of glaucoma.

Choroidal capillary and venous congestion in central serous chorioretinopathy.

PURPOSE: Abnormalities in choroidal perfusion have been hypothesized to be causative factors in central serous chorioretinopathy. This prospective study was performed to evaluate changes in the choroidal circulation in cases of central serous chorioretinopathy. METHODS: In 32 consecutive patients with acute or chronic recurrent central serous chorioretinopathy, complete clinical ophthalmologic examinations, fluorescein angiography, and indocyanine green angiography with a scanning laser ophthalmoscope and a digital imaging system were performed. RESULTS: All patients with acute and chronic recurrent central serous chorioretinopathy demonstrated a localized delay in arterial filling followed by choroidal hyperperfusion in the area of the damaged retinal pigment epithelium, frequently associated with dilated capillaries and dilated draining venules in one or more choroidal lobules. These changes corresponded to areas with pigment epithelial detachment or focal leakage from the retinal pigment epithelium found in fluorescein angiography. Furthermore, in some patients, localized choroidal ischemia could be observed in additional areas throughout the central fundus in both diseased eyes and normal fellow eyes. CONCLUSIONS: Delayed arterial filling followed by capillary and venous hyperemia, angiographically appearing as capillary and venous congestion, can be observed frequently in eyes with central serous chorioretinopathy. The results suggested that capillary or venous congestion after ischemia in one or more choroidal lobules might be the reason for the choroidal hyperpermeability associated with central serous chorioretinopathy.

Gliosis-like retinal alterations in glaucoma patients.

SUMMARY: Morphological alterations resembling fine epiretinal gliosis in the midperiphery of the retina of glaucoma patients were examined biomicroscopically. Examination with a laser-scanning ophthalmoscope (Zeiss CLSO) incorporating an argon laser confirmed sharply bordered, patchy retinal alterations in the superficial layers. These alterations were predominantly in the Bjerrum area but did not conform to the shape of the nerve fiber bundles. Patchy retinal alterations were found to be absent or rare in nonglaucomatous controls (0 of 15 controls) but to occur quite often in people with glaucoma. Although all glaucoma patients examined had typical optic nerve heads and visual field damage, the prevalence of patchy retinal alterations was especially high in the group with progressive damage despite successfully reduced intraocular pressure (13 of 15; 86.7%); the alterations were only slightly less prevalent in the normal-tension-glaucoma group (11 of 16; 68.8%).

Influence of acquisition parameters on hemodynamic measurements with the Heidelberg Retina Flowmeter at the optic disc.

PURPOSE: The Heidelberg Retina Flowmeter (HRF; Heidelberg Engineering GmbH, Heidelberg, Germany) is a new instrument that determines hemodynamic variables at discrete locations of the retina and the optic disc. The objective of this study was to evaluate the influence of various HRF recording settings on the long-term variability of the HRF parameter. "Flow," computed at the optic nerve head in healthy individuals. METHODS: The authors obtained 2 sets of 5 HRF recordings in 10 healthy individuals (age range, 23-60 years). The HRF recordings were obtained within a scan area of 10 degrees x 2.5 degrees (set 1) and 20 degrees x 5 degrees (set 2). For each set, the HRF recordings were obtained on 5 consecutive days. Respective HRF recordings for both sets were obtained on the same days. On these recordings, the HRF parameter, "Flow," was computed at 3 different regions of interest (temporal superior, temporal inferior, and temporal rim of the optic disc). At all three locations, Flow was computed within windows of measurement of 10 pixels x 10 pixels and 20 pixels x 20 pixels. The effect of larger windows (30 pixels x 30 pixels, 40 pixels x 40 pixels, and 50 pixels x 50 pixels) was tested at the temporal rim of the optic disc. RESULTS: The highest reliability coefficient was reached with a scan area of 20 degrees x 5 degrees at the temporal superior rim of the optic disc (r = 0.93). Within a scan area of 20 degrees x 5 degrees, the size of the user-defined measuring window did not influence the reliability. Two models of analysis of variance disclosed that the only effect on the computed value of Flow that reached statistical significance was that because of the scan area (F = 11.172; p = 0.001). The location of the window of measurement and its size had no statistically significant effect. CONCLUSION: The present results show that the location of the window of measurement has an important effect on the long-term variability of the HRF parameter, Flow. In addition, different scan areas influence significantly the computed values of this parameter.

Descriptive information of topographic parameters computed at the optic nerve head with the Heidelberg retina tomograph.

PURPOSE: To analyze the frequency distribution and descriptive information of topometric data obtained with the Heidelberg Retina Tomograph (HRT) in a normal population. METHODS: Topographic measurements of the optic disc were acquired and evaluated using the HRT in 225 subjects between 12 and 90 years of age. After randomly selecting one eye per subject, the frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles were evaluated for topographic parameters computed by the HRT. The influence of age, intraocular pressure (IOP), disc size, and disc shape on optic disc topometric data was analyzed. A principal component analysis of the topometric parameters was performed. The frequency distributions, mean values, minima, maxima, and first, fifth, fiftieth, ninety-fifth, and ninety-ninth percentiles of the interocular difference in topographic parameters were evaluated. RESULTS: All topographic parameters showed a unimodal but not necessarily normal distribution. None of the parameters showed a relevant correlation with age, IOP (in the normal range), and overall shape of the anterior optic nerve, but a few parameters showed a clinically significant correlation with disc size. A principal component analysis identified four relevant factors (optic nerve cup, retinal nerve fiber layer, optic disc size, and optic nerve cup shape) in the entire data set of optic nerve topometric data. The absolute value of all interocular differences in topographic parameters showed an asymmetric but unimodal distribution. CONCLUSION: The mathematical description of the optic nerve cup shape provides information on optic nerve head topography independently from cupping, nerve fiber layer thickness, and disc size. Potentially, quantification of further aspects in optic nerve head topography might improve the discriminatory power of computerized quantitative optic nerve head analysis.

Interocular differences in optic disc topographic parameters in normal subjects.

PURPOSE: To test the interocular differences in optic disc topography in normal subjects by means of confocal scanning laser ophthalmoscopy. METHODS: Topographic measurements of the optic disc were evaluated by means of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph) in 314 eyes of 157 healthy volunteers. The examination was started randomly either with the right eye or the left eye. Differences between right and left eyes in disc area, cup area, cup volume, cup/disc area ratio, rim area, rim volume, maximum cup depth, cup shape measure, retinal nerve fiber layer thickness, and retinal nerve fiber cross section area for 360 degrees and for the temporal and nasal regions of the optic nerve head were evaluated by means of Student t-test. The same parameters were assessed in a subgroup of 80 elderly (age> 50 years) healthy subjects. Holm's sequentially rejective method was used for significance correction of multiple comparisons. RESULTS: Significant interocular differences in the average retinal nerve fiber layer thickness (p = 0.0010) and retinal nerve fiber layer cross section area (p = 0.0036) were found, with the right eye showing, on the average, lower values. The left eye showed a larger retinal nerve fiber layer thickness in 94 subjects (59.87%) and a larger retinal nerve fiber cross section area in 101 subjects (64. 33%). In the temporal optic disc area there were no statistically significant differences in topometric data (p> 0.05). In the nasal area, significant interocular differences in the retinal nerve fiber layer thickness (p = 0.0002) and retinal nerve fiber layer cross section area (p = 0.0003) were found. Similar results were found when the group of subjects older than 50 years was considered. CONCLUSIONS: This study demonstrates systematic interocular differences in optic disc topometric data. Such a finding, be it due to methodological or biological reasons, should be taken in consideration in clinical trials.

Iris transillumination defects in patients with primary open angle glaucoma.

PURPOSE: To examine the incidence and pattern of iris transillumination defects in patients with primary open angle glaucoma (POAG) with and without vascular dysregulation, in comparison to controls. METHODS: We prospectively examined 24 patients with POAG (M/F 10:14; mean age 59 +/- 14, range 21-76 years) and 23 controls (M/F 10:13; mean age 52 +/- 15, range 25-86 years). Vascular dysregulation was presumed if patients had a typical medical history of vasospasm and a pathological result in nailfold capillaroscopy. Iris transillumination defects were visualized by video-taped, digitized diaphanoscopy and assessed by two blinded observers. RESULTS: We found significantly more iris transillumination defects in POAG than in controls (54.2% vs. 8.7%; chi2 = 8.85; df = 1; p = 0.002). The defects in POAG showed a characteristic radially-streaked pattern different from those described, for instance, in pigment dispersion syndrome, pseudoexfoliation syndrome, and acute glaucoma. Glaucoma patients with vascular dysregulation had a tendency to a higher incidence of transillumination defects than non-vasospastic patients, though this finding was not significant. CONCLUSIONS: Patients with POAG have a higher incidence of iris transillumination defects than controls. The underlying mechanisms are not yet clear and call for further investigation.

Multicenter evaluation of tendency-oriented perimetry (TOP) using the G1 grid.

PURPOSE: The G1-TOP program is a short automated perimetric strategy which sub-divides the G1 grid of 59 points into four sub-grids. Each point is tested only once, but each patient's response is used to modify that particular point and the surrounding ones from the remaining sub-grids. This study compared the results of the G1-TOP program with the Standard Bracketing strategy. METHODS: Eleven participating institutions provided data from 213 patients (406 eyes). The main group consisted of 284 glaucomas and 55 glaucoma suspects. Other groups included 31 eyes with neurological disorders, 20 with chorioretinal lesions and 16 normal eyes. Mean age was 62.7 +/- 15.4 (range 14-88) years. All subjects had previous perimetric experience and visual acuity better than 0.5. Examination included G1-Standard Bracketing and G1-TOP testing, in interchangeable order, with the Octopus 1-2-3 perimeter. RESULTS: The correlation coefficient for mean defect (MD) was 0.95. Standard error (YX) for MD, square root of loss variance (LV) and individual thresholds were 1.86 dB, 1.29 dB, and 4.72 dB, respectively. Mean sensitivity values were similar (difference 0.04 +/- 1.87 dB) (p>0.05). Mean duration for G1-TOP was 2.19 +/- 0.26 min, while G1-Standard Bracketing took 11.51 +/- 1.52 min (ratio 1/5.1, or a net reduction of 80.4%). The sensitivity of G1-TOP versus G1-Standard Bracketing was: glaucoma 77.1/78.5, glaucoma suspects 38.2/47.3, neurological disorders 87.1/87.1 and chorioretinal lesions 80.0/85.0. CONCLUSIONS: The G1-TOP program gave very similar results to G1-Standard Bracketing in only 20% of the time required by the standard strategy.

Topical SDZ GLC-756, a novel dopamine D-1 antagonist and D-2 agonist, lowers intraocular pressure in conscious rabbits.

This investigation was carried out to evaluate the effect of SDZ GLC-756, a novel dopamine D-1 antagonist and D-2 agonist, on intraocular pressure (IOP) in rabbits. A randomized, placebo-controlled, double-masked, crossover study with topical application of SDZ GLC-756 eyedrops [0.015% (n = 10), 0.03% (n = 10), 0.0625% (n = 10), 0.125% (n = 9), 0.25% (n = 10), 0.5% (n = 14)] and vehicle alone (placebo-control) to the right eye was performed in New Zealand White rabbits. The contralateral eye received no treatment. IOP was measured using a pneumatonometer. Topical SDZ GLC-756 significantly lowered IOP in a dose-dependent manner (maximal IOP-lowering effect 1 approximately 2 hours after administration) in the treated eye and, to a lesser extent, in the contralateral eye. The duration of action was approximately 4 hours. The simultaneous D-1 antagonistic and D-2 agonistic properties of SDZ GLC-756 may provide a new pharmacological approach to the treatment of glaucoma, which deserves further investigation.

The influence of sex difference in measurements with the Langham Ocular Blood Flow System.

PURPOSE: To assess sex difference and parameters possibly accounting for such a difference in healthy subjects evaluated by means of the Langham Ocular Blood Flow (OBF) System. METHODS: Pulse amplitude of intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were assessed in 86 healthy men and 69 healthy women. RESULTS: Compared to men, women showed higher POBF (mean +/- SD: 722.6 +/- 152.8 versus 647.8 +/- 164.9 microL/min; P =.0056) and pulse amplitude (mean +/- SD: 2.3 +/- 0.7 versus 2.0 +/- 0.6 mm Hg; P =.0043) values. Sex difference was still significant after correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse amplitude correlated negatively with pulse rate, and POBF correlated negatively with IOP. Women had higher readings in pulse amplitude and POBF, even after correcting for age, refraction, IOP, blood pressure, and pulse rate. CONCLUSIONS: While using the Langham OBF System, one needs to be aware of sex difference that is independent of other hemodynamic parameters. How the observed difference in POBF is related to ocular blood flow, and how it might influence the preponderance of various ocular diseases in men or women remains to be clarified.

[Model experiments of the outer blood-retinal barrier in vitro]. / Modellexperimente zur äusseren Blut-Retina-Schranke in vitro.

Because of the difficulty in conducting experiments on the outer blood-retinal barrier in vivo, we developed an in vitro model. Bovine retinal pigment epithelial cells were grown on semipermeable membranes, enabling separate manipulation of the apical and basal medium. As a parameter of barrier function, we measured the transepithelial resistance (TER). Barrier function was also tested with fluorescein. The transepithelial resistance increased under optimal culture conditions, in confluent cultures, by 200 omega and there was no fluorescein leakage. After exposure to trypsin in Ca/Mg-less medium or EDTA or after application of argon laser, we were able to induce a breakdown of the TER and fluorescein leakage. This happened immediately after laser exposure, 1 min after EDTA, and 4 min after trypsin application. We observed no morphological differences after breakdown of the barrier function on the intercellular connections compared to normal confluent cultures following EDTA or trypsin exposure. In all experiments there was a recovery of barrier function after returning the cells to control conditions. These first results demonstrate that our in vitro model is a sensitive method for investigating barrier function in retinal pigment epithelium in cell culture.

[Influence of postoperative oral steroid treatment on retinal sensitivity in patients after macular surgery. A randomized, controlled, clinical trial]. / Einfluss postoperativer oraler Steroidgabe auf die retinale Sensitivität bei Patienten nach Makulachirurgie. Eine randomisierte, kontrollierte, klinische Studie.

BACKGROUND: The aim of this study was to evaluate the effect of postoperative systemic steroid treatment on retinal sensitivity in patients with epiretinal membrane (ERM) after successful surgery. PATIENTS AND METHODS: A total of 28 patients with ERM, macular edema and visual loss were included in this study. All patients were treated with combined 23 gauge vitrectomy and peeling of the ERM and inner limiting membrane (ILM). After randomization the first group (n = 14) was treated with postoperative systemic steroids (100 mg prednisolone per day for 5 days) and the second group (n = 14) served as a control group. Follow-up examinations were performed up to 12 months. RESULTS: After 12 months a statistically significant increase in visual acuity with a gain of 17/10 letters in the steroid/control group as well as significant decrease of the central retinal thickness of 107/128 µm could be observed (p < 0.05). In the steroid/control group mean retinal sensitivity increased from 14.0/14.3 dB after 12 months in comparison to 11.7/11.9 dB at baseline examination (p < 0.05). CONCLUSIONS: Postoperative oral steroid treatment does not seem to be beneficial in patients with macular pucker surgery.

New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel.

The current standard therapy for patients with diabetic macular oedema (DME)--focal/grid laser photocoagulation--usually does not improve impaired vision, and many patients lose vision despite laser therapy. Recent approval of ranibizumab by the European Medicines Agency to treat visual impairment due to DME fulfils the previously unmet medical need for a treatment that can improve visual acuity (VA) in these patients. We reviewed 1- and 2-year clinical trial findings for ranibizumab used as treatment for DME to formulate evidence-based treatment recommendations in the context of this new therapy. DME with or without visual impairment should be considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria for clinically significant oedema. For DME with centre involvement and associated vision loss due to DME, monthly ranibizumab monotherapy with treatment interruption and re-initiation based on VA stability is recommended. Laser therapy based on ETDRS guidelines is recommended for other forms of clinically significant DME without centre involvement or when no vision loss has occurred, despite centre involvement. Because these recommendations are based on randomised controlled trials of 1-2 years duration, guidance may need updating as long-term ranibizumab data become available and as additional therapeutic agents are assessed in clinical trials.

Use of systemic steroid after successful macular surgery in eyes with epiretinal membrane: a randomized, controlled clinical study.

PURPOSE: To evaluate the functional and morphological outcomes of postoperative systemic steroid therapy after successful macular surgery in eyes with macular edema due to idiopathic macular epiretinal membranes (ERMs). DESIGN: Prospective, randomized, investigator-masked, controlled clinical study. METHODS: Twenty-eight patients scheduled for 23-gauge vitrectomy combined with ERM and inner limiting membrane (ILM) peeling for macular edema due to ERM were included in this single center trial. Patients were randomized to receive oral steroid therapy (Prednisolone, 100 mg per day for 5 days) or no oral steroid (control group) after surgery. Main outcome measures included best corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), central retinal thickness (CRT), retinal volume (RV), and macular morphology as determined by spectral domain optical coherence tomography (SD-OCT, Cirrus). Examinations were carried out preoperatively and at week 1, at months 1 and 3, postoperatively. RESULTS: At month 3, mean BCVA improved to a eight-letter gain in each study group (P<0.01 compared with baseline for both groups), showing no statistically significant difference between both the groups (P=0.19). Morphologically, retinal surface folds resolved within 1 month after surgery in both treatment groups, followed by a progressive recovery of retinal layer integrity and a statistical significant (P<0.01) decrease in CRT and RV without significant differences between both groups (P=0.62, P=0.13, respectively, ANOVA between the groups). CONCLUSION: The early postoperative use of systemic steroid treatment after successful vitrectomy combined with ERM and ILM peeling does not seem to improve significantly the anatomic and functional outcomes in eyes with ERM.

Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials.

BACKGROUND: Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. METHODS: An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. RESULTS: Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. CONCLUSION: Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

Morphological and functional analysis of the loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration.

AIM: To quantify and correlate the morphological and functional effects of the recommended loading regimen with intravitreal ranibizumab in neovascular age-related macular degeneration (AMD). METHODS: In a prospective, interventional clinical trial, 29 consecutive patients (29 eyes) with choroidal neovascularisation secondary to AMD received three initial monthly intravitreal injections of ranibizumab. During this loading regimen, best corrected visual acuity (BCVA) and microperimetry (MP) testing, as well as optical coherence tomography and fluorescein angiography (FA), were performed using a standardised protocol and the results correlated. RESULTS: Significant morphological and functional therapeutic effects were observed as early as 1 week following the first treatment. Throughout the loading-dose period, central retinal thickness, including intraretinal cysts and subretinal fluid, decreased fast and significantly (p<0.01); pigment epithelial detachment resolved less rapidly. The mean leakage area by FA decreased (p<0.01) and retinal function (BCVA and MP) increased significantly (both p<0.01). However, the change in morphology and function was only significant between baseline and week 1. There was no significant additional morphological or functional benefit following the second and third injection. CONCLUSION: The initial administration of intravitreal ranibizumab in neovascular AMD induced a significant effect on intra- and subretinal fluid and visual function; subsequent injections had a less pronounced effect. It remains to be determined whether this loading regimen should be mandatory in all patients or if a single dose regimen would lead to a comparable functional and morphological retinal improvement.