Fred Hendrikse

Astigmatism management in cataract surgery with the AcrySof toric intraocular lens.

PURPOSE: To present clinical data from a single‐center prospective clinical trial of the AcrySof toric intraocular lens (IOL). SETTING: Academic Hospital Maastricht, Maastricht, The Netherlands. METHODS: Fifty‐three eyes (43 patients) had implantation of an AcrySof toric IOL. Three toric models were evaluated in cylinder powers of 1.50 diopters (D) (SN60T3; T3 group, n = 16), 2.25 D (SN60T4; T4 group, n = 14), and 3.00 D (SN60T5; T5 group, n = 23) at the IOL plane. The T5 group was subdivided into eyes that could be fully corrected (T5a, n = 13) and eyes that could be partially corrected (T5b, n = 10). RESULTS: Four months postoperatively, the mean uncorrected visual acuity (UCVA) was 0.77 ± 0.23 in the T3 group, 0.93 ± 0.23 in the T4 group, 0.82 ± 0.15 in the T5a group, and 0.47 ± 0.13 in the T5b group. More than 90% of the combined eyes in the T3, T4, and T5a groups achieved a UCVA of 20/40 or better, and almost 80% achieved a UCVA of 20/25 or better. Residual refractive astigmatism of less than 0.75 D was achieved in 74% of eyes and of less than 1.00 D in 91%. The mean IOL misalignment was 2.5 ± 2.1 degrees in the T3 group, 3.5 ± 2.3 degrees in the T4 group, and 4.1 ± 3.5 degrees in the T5 group. CONCLUSION: Implantation of the AcrySof toric IOL proved to be an effective, safe, and predictable method of managing corneal astigmatism in cataract patients.

Vitrectomy results in diabetic macular oedema without evident vitreomacular traction

Abstract.Purpose: To determine the effectiveness of vitrectomy in eyes with diabetic macular oedema without evident traction from a thickened vitreous membrane. Methods: Twenty-one consecutive eyes from 19 patients with diabetic macular oedema that had undergone vitrectomy were analysed retrospectively. All eyes had an attached posterior hyaloid membrane in the macular region, but without thickening and without evident traction on the macula. A standard pars plana vitrectomy with the creation of a posterior vitreous detachment was performed. Results: Median duration of macular oedema at the time of vitrectomy was approximately 11.0 months (range 2–36 months). The median preoperative best-corrected visual acuity of 0.08 (range hand motions/0.003 to 0.4), improved by 5 lines to a median final postoperative best-corrected visual acuity of 0.25 (range 0.025–0.5) (P=0.001). Seven eyes without preoperative macular photocoagulation had a median visual acuity improvement of 77%, range 32–400%, while 12 eyes with preoperative macular laser treatment had a median visual acuity improvement of 14.8%, range 0–66.1% (P=0.02, CI 95%, after multivariate regression analysis). In all 21 eyes, macular oedema was no longer visible on microscopic examination after a median period of 3.0 months (range 1–9 months) after vitrectomy. Conclusions: In eyes with diabetic macular oedema without evident macular traction from a thickened vitreous membrane, vitrectomy resulted in the resolution of macular oedema, with an improvement in visual acuity in the majority of cases. Eyes without preoperative macular photocoagulation had a significantly higher percentage visual improvement than eyes without preoperative macular laser treatment. A randomised controlled prospective trial of primary vitrectomy versus macular photocoagulation is needed to determine the role of vitrectomy as treatment modality for diabetic macular oedema.

Immunological Factors in the Pathogenesis and Treatment of Age-Related Macular Degeneration

Recent findings indicate that immunological factors are involved not only in the pathogenesis of age-related macular degeneration (AMD), but also in its treatment. Earlier data showing the presence of inflammatory cells in affected areas of AMD retinas support this statement. Although a possible role for autoimmunity was initially suggested, it has never reached general acceptance. Microorganisms have also been implied in the pathogenesis of AMD. Both serum antibacterial antibody levels and positive DNA tests from neovascular membranes have pointed to a possible role for Chlamydia pneumoniae in the pathogenesis of AMD. New data is providing evidence for the hypothesis that deposits between Bruchs membrane and the retinal pigment epithelium (RPE) cell layer may act as a stimulus for the local activation of the complement system. This may lead to a further growth of the deposits due to the strong chemotactic activity of certain complement activation products (such as C5a) with an influx of inflammatory cells. The buildup of cells and extracellular deposits may lead to local ischemia resulting in the activation of RPE cells. These activated RPE cells are thought to release angiogenic stimuli leading to choroidal neovascularization, which is the most serious complication of AMD. The fact that immunosuppressive drugs such as triamcinolone acetonide and anecortave acetate are capable of inhibiting choroidal neovascularization is consistent with an inflammatory component in the pathogenesis of AMD. Specific immunotherapy directed at certain cytokines or growth factors is now being investigated at both the animal and patient levels. Various clinical trials involving engineered antibodies are now being applied to block angiogenic factors such as the vascular endothelial growth factor (VEGF). An approach using gene therapy to influence angiogenesis by inducing the production of the pigment epithelium-derived factor (PEDF) was able to block neovascularization in an experimental murine model. Besides trying to block ongoing processes in AMD, retinal transplantation is now also being investigated as a treatment option. The fact that the retina is possibly an immunoprivileged tissue in combination with experimental data showing that the subretinal space is an immunoprivileged site is an indication that transplantation would not suffer from the rejection process. A larger obstacle is the question whether transplanted retinal tissue will regain its functional properties.

The relationship between visual field loss in glaucoma and health-related quality-of-life

PurposeTo investigate the relationship between visual field loss and health-related quality-of-life (HRQOL) in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG).MethodsWe conducted a cross-sectional study among 537 OHT and POAG patients from seven hospitals in The Netherlands. Clinical information was obtained from medical files. Patients completed a questionnaire, containing generic HRQOL instruments (EQ-5D and Health Utilities Index mark 3), vision-specific National Eye Institute Visual Functioning Questionnaire (VFQ-25), and glaucoma-specific Glaucoma Quality-of-Life questionnaire (GQL-15). The impact of visual field loss on HRQOL scores was analysed with multiple linear regression analyses.ResultsA relationship between mean deviation (MD) and HRQOL was found after adjusting for age, gender, visual acuity, medication side effects, laser trabeculoplasty, and glaucoma surgery. We found interaction between MD in both eyes for GQL and VFQ-25 scores. The relationship between MD and utility was non-linear, with utility only affected at MD-values below −25 dB in the better eye. Visual acuity, side effects, and glaucoma surgery independently affected HRQOL. Binocular MD and MD in the better eye had similar impacts on HRQOL, whereas MD in the worse eye had an independent effect. HRQOL was affected more by binocular defects in the inferior than in the superior hemifield.ConclusionVisual field loss in progressing glaucoma is independently associated with a loss in both disease-specific and generic quality-of-life. It is important to prevent progression, both in early and in advanced glaucoma, especially in patients with inferior hemifield defects and severe defects in either eye.

A Systematic Review Of The Adverse Events Of Intravitreal Anti-vascular Endothelial Growth Factor Injections

Background: Intravitreal ranibizumab and pegaptanib are registered for neovascular age-related macular degeneration. No formal safety study has been conducted for intravitreal bevacizumab. These anti-vascular endothelial growth factor (anti-VEGF) drugs are being used on a large scale in daily practice for different ocular diseases. The objective of the present study was to systematically assess and compare the incidences of adverse events of anti-VEGFs. Methods: A systematic search was conducted in April 2009 with no date restrictions in PubMed, Embase, Toxline, and the Cochrane library. We used the terms pegaptanib, bevacizumab, ranibizumab, intravitreal, and specific and general terms for adverse events. Studies describing adverse events after anti-VEGF injections and the official safety data were included. Results: Two hundred and seventy-eight articles were included, and the incidences of adverse events were calculated separately for effect, safety, and specific side effect studies. The incidences of serious ocular and nonocular adverse events were approximately below 1 per 100 injections for intravitreal bevacizumab, intravitreal ranibizumab, and intravitreal pegaptanib. Most mild ocular adverse events were below 5 per 100 injections. Conclusion: The reported rates of serious adverse events were low after anti-VEGF injections. There is no sufficient evidence to conclude that there is a difference in incidences between the anti-VEGFs.

Intraocular straylight after implantation of the multifocal AcrySof ReSTOR SA60D3 diffractive intraocular lens.

PURPOSE: To measure intraocular straylight (as a measure of glare) after cataract surgery and implantation of an AcrySof ReSTOR SA60D3 multifocal or AcrySof SA60AT monofocal intraocular lens (IOL) (both Alcon Laboratories). SETTING: University Hospital Maastricht, Maastricht; Isala Clinics, Zwolle; Netherlands Institute for Neurosciences, Amsterdam, The Netherlands. METHODS: In a prospective open observational case series, a newly developed straylight meter was used to objectively measure straylight 6 months postoperatively in 66 eyes with a diffractive AcrySof ReSTOR SA60D3 IOL (multifocal group) and 40 eyes with a monofocal AcrySof SA60AT IOL (monofocal group). A comparison of straylight levels in an age‐matched population without cataract (control group) was performed. RESULTS: The straylight level was 1.20 log units ± 0.16 (SD) in the multifocal group and 1.10 ± 0.19 log units in the monofocal group. When the difference in mean level of straylight was adjusted for age, mean straylight levels were 0.078 log units lower in the monofocal group than in the multifocal group (P = .026). Straylight levels in both pseudophakic groups were lower than in the control group without cataract (P<.0001). CONCLUSIONS: Levels of intraocular straylight log(s) were significantly lower for both types of IOL than in age‐matched subjects from the normal population. The mean level of intraocular straylight 6 months postoperatively was higher in patients with an AcrySof ReSTOR SA60D3 IOL than in patients with a monofocal AcrySof SA60AT IOL. Implantation of the former IOL would therefore result in a smaller gain in contrast sensitivity and a smaller reduction in glare and halos than implantation of the latter IOL.

Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty

OBJECTIVE To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

In Vitro Human Scleral Permeability of Fluorescein, Dexamethasone-Fluorescein, Methotrexate-Fluorescein and Rhodamine 6G and the Use of a Coated Coil as a New Drug Delivery System

PURPOSE To determine the in vitro human scleral permeability of several dyes and drugdye combinations with varying molecular weights (MW) and lipid solubilities (fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein, and rhodamine). Coils coated with rhodamine were also evaluated for scleral permeability and sustained release. METHODS Scleral sections excised from moist chamber stored human globes were mounted in a 2-compartment perfusion chamber. A small depot of drug/dye (100 microl of 10(-4) M fluorescein, dexamethasone-fluorescein, methotrexate-fluorescein or rhodamine) or a coated coil in 100 microl of BSS was added to the episcleral surface while perfusing BSS to the choroidal side. The perfusate was collected and measured for fluorescence. Permeability was calculated as Ktrans from the flux measurements. RESULTS Ktrans values (cm/sec, mean +/- SE) for the studied dyes and drug-dye combinations were 5.21 +/- 0.71 x 10(-6) for fluorescein, 1.64 +/- 0.17 x 10(-6) for dexamethasone-fluorescein, 3.36 +/- 0.62 x 10(-6) for methotrexate-fluorescein, 1.86 +/- 0.39 x 10(-6) for rhodamine and 2.18 +/- 0.23 x 10(-6) for the rhodamine from the coils. We found a significant difference between the permeability of the sclera to fluorescein and dexamethasone-fluorescein (P < 0.001), methotrexate-fluorescein (P < 0.05) and rhodamine (P < 0.001). Steady state flux was observed from the rhodamine coil. CONCLUSION The rank order of scleral permeability to the studied dyes is as follows: fluorescein > methotrexate-fluorescein > rhodamine coil > rhodamine 6G > dexamethasone-fluorescein. Differences in scleral permeability are related to MW and lipid solubility. Prolonged transscleral diffusion of rhodamine delivered by solution and by coil are similar.

An evidence-based review of prognostic factors for glaucomatous visual field progression.

PURPOSE To examine which prognostic factors are associated with glaucomatous visual field progression. DESIGN Knowledge of prognostic factors helps clinicians to select patients at risk of glaucomatous visual field progression and intensify their treatment. METHODS By consulting relevant databases, we identified 2733 articles published up to September 2010, of which 85 articles investigating prognostic factors for visual field progression in patients with open-angle glaucoma (OAG) were eligible. We summarized results for each factor in tables, noting the direction of the association between the prognostic factor and progression, and the accompanying P value. Four authors, working blind to the factors, independently judged the extent to which a prognostic factor was associated with glaucomatous visual field progression. If there were different associations for normal-tension glaucoma (NTG) studies, they were judged separately. Consensus was reached during group meetings. MAIN OUTCOME MEASURES A ranking of all studied prognostic factors for glaucomatous visual field progression according to their likelihood of being prognostic. RESULTS A total of 103 different prognostic factors were investigated in 85 articles. The following factors were clearly associated with glaucomatous visual field progression: age, disc hemorrhages (for NTG), baseline visual field loss, baseline intraocular pressure (IOP), and exfoliation syndrome. An association was unlikely for family history of glaucoma, atherosclerosis, systemic hypertension, visual acuity, sex (for NTG), systolic blood pressure, myopic refractive error (for NTG), and Raynauds phenomenon. CONCLUSIONS The factors we found clearly associated with progression could be used in clinical practice and for developing clinical prediction models. For many other factors, further research is necessary.

A network meta-analysis combined direct and indirect comparisons between glaucoma drugs to rank effectiveness in lowering intraocular pressure

OBJECTIVE It is difficult to rank treatments according to their effect size when several treatments are available and not all treatments have been compared directly. The purpose of this study was to show a new statistical technique (network meta-analysis) to address this problem and to rank glaucoma drugs according to their intraocular pressure (IOP)-reducing effect. STUDY DESIGN AND SETTING Network meta-analysis of randomized controlled trials was used to combine direct and indirect estimates of the effect of eight drugs and placebo from 28 randomized controlled trials in patients with primary open-angle glaucoma or ocular hypertension patients, 6,841 for the peak effect and 6,953 patients for the trough effect. RESULTS All drugs differ from placebo in lowering IOP. At the peak, the rank order from high to low in terms of the mean IOP reduction reached is bimatoprost, travoprost and latanoprost, brimonidine, timolol, dorzolamide, betaxolol, brinzolamide. At the trough, this rank order is bimatoprost, latanoprost, travoprost, timolol, betaxolol, dorzolamide, brinzolamide, brimonidine. The results based on direct or indirect estimates were similar. This ranking differed from the ranking based on the mean IOP change from baseline of all arms including the study drug from all randomized controlled trials. CONCLUSIONS A network meta-analysis can be used to combine direct and indirect treatment effects in a formal way. Applied to glaucoma medications, it shows that there is a rank order in treatment effects on IOP.