Nicolas Feltgen

Correlation between central corneal thickness, applanation tonometry, and direct intracameral IOP readings

BACKGROUND Several authors reported incorrect high intraocular pressure (IOP) values in eyes with a thick cornea using applanation tonometry. This hypothesis was checked by comparing applanation tonometry with direct intracameral manometry. METHODS 73 patients, scheduled for intraocular surgery, were enrolled. Immediately before surgery, the following were registered: (i) central corneal thickness (CCT), (ii) applanatory IOP (Perkins/Tonopen), and (iii) intracameral IOP. RESULTS The difference between applanatory and intraocular measurements was completely independent of CCT (y=−3.43+3.8x; where y is the difference between applanatory and intracamerally measured IOP (mm Hg) and x is CCT (mm);r 2=0.002; p=0.72). CONCLUSIONS There is no systematic error of applanation tonometry with increasing CCT. Therefore it is inadequate to recalculate IOP based on regression formula of applanatory IOP versus CCT.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review.

Background Intravitreal agents have replaced observation in macular edema in central (CRVO) and grid laser photocoagulation in branch retinal vein occlusion (BRVO). We conducted a systematic review to evaluate efficacy and safety outcomes of intravitreal therapies for macular edema in CRVO and BRVO. Methods And Findings: MEDLINE, Embase, and the Cochrane Library were systematically searched for RCTs with no limitations of language and year of publication. 11 RCTs investigating anti-VEGF agents (ranibizumab, bevacizumab, aflibercept) and steroids (triamcinolone, dexamethasone implant) with a minimum follow-up of 1 year were evaluated. Efficacy: CRVO Greatest gain in visual acuity after 12 months was observed both under aflibercept 2 mg: +16.2 letters (8.5 injections), and under bevacizumab 1.25 mg: +16.1 letters (8 injections). Ranibizumab 0.5 mg improved vision by +13.9 letters (8.8 injections). Triamcinolone 1 mg and 4 mg stabilized visual acuity at a lower injection frequency (-1.2 letters, 2 injections). BRVO Ranibizumab 0.5 mg resulted in a visual acuity gain of +18.3 letters (8.4 injections). The effect of dexamethasone implant was transient after 1.9 implants in both indications. Safety Serious ocular adverse events were rare, e.g., endophthalmitis occurred in 0.0-0.9%. Major differences were found in an indirect comparison between steroids and anti-VEGF agents for cataract progression (19.8-35.0% vs. 0.9-7.0%) and in required treatment of increased intraocular pressure (7.0-41.0% vs. none). No major differences were identified in systemic adverse events. Conclusions Anti-VEGF agents result in a promising gain of visual acuity, but require a high injection frequency. Dexamethasone implant might be an alternative, but comparison is impaired as the effect is temporary and it has not yet been tested in PRN regimen. The ocular risk profile seems to be favorable for anti-VEGF agents in comparison to steroids. Because comparative data from head-to-head trials are missing currently, clinicians and patients should carefully weigh the benefit-harm ratio.

Functional and anatomical results after a single intravitreal Ozurdex injection in retinal vein occlusion: a 6-month follow-up – The SOLO study

Purpose: To evaluate the efficacy of intravitreal dexamethasone implants in eyes with cystoid macular oedema (CME) secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in the clinical everyday practice, examine the effects of early retreatment and compare the results with the GENEVA study.

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study (SPR Study): recruitment list evaluation. Study report no. 2.

BackgroundAccompanying the patient recruitment within the “Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment multicentre trial (SPR)”, all patients with primary rhegmatogenous retinal detachment (RRD) had to be documented in a detailed recruitment list. The main goal of this analysis was to estimate the prevalence of “medium-severe” RRD (SPR Study eligible) as defined by the SPR Study inclusion criteria. In addition, the detailed anatomical situation of medium-severe RRD is investigated.MethodsSPR Study recruitment was evaluated via a standardised questionnaire, which contained a coloured fundus drawing and information regarding possible reasons for exclusion from the SPR Study in each case. A team of three experienced vitreoretinal surgeons evaluated all fundus drawings from a 1-year period. The review led to a decision on SPR Study eligibility on the pure basis of anatomical assessment. The main outcome measures were assessment of feasible inclusion into the SPR Study by the evaluation team based on the fundus drawing and anatomical details.ResultsA total of 1,115 patients with RRD from 13 European centres were prospectively enrolled in the year 2000. The quality of the drawings sufficed for assessment in 1,107 cases (99.3%). Three hundred and twelve fundus drawings (28.2%) met the anatomic inclusion criteria of the SPR Study. RRD of medium severity is characterised by an average number of 2.6 (SD 2.4) retinal breaks, 5.8 (SD 2.8) clock hours of detached retina, unclear hole situation in 15.1% of cases (n=47), attached macula in 42.9% (n=134), bullous detachment in 15.1% (n=47) and vitreous haemorrhage/opacity in 7.7% (n=24).ConclusionsIn the recruitment lists of the SPR Study of the year 2000, RRD of medium severity was present in nearly one third of the patients with primary RRD. These findings emphasise the clinical relevance of the SPR Study.

Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters

PurposeTo investigate the correlation between estrogen receptor-positive basal cells of the meibomian glands of the lower lid with age, gender, and subjective and objective dry-eye parameters.MethodsSixteen lower lid specimens were collected from 7 female and 9 male patients (age range 22–88 years) during tumor surgery requiring whole-thickness excision. Prior to surgery the patients were asked about any dry-eye symptoms (score 0–4, where 0= no dry-eye symptoms). Tear break-up time was measured, and Schirmer I and II tests were performed. We obtained histological sections from the outer margins of the formalin-fixed and paraffin-embedded specimens and performed immunohistochemical staining for estrogen, progesterone and androgen receptors. At least 500 cells were counted per specimen, and the proportion of positively stained cells was calculated and correlated to the age and dry-eye parameters.ResultsAll meibomian glands had positive nuclear staining with antibodies for estrogen receptors in their outer cell layers, i.e., the basal cell layer. The proportion of cells expressing estrogen receptors increased with age independent of gender (correlation coefficient=0.67, P<0.005). No correlation was found between estrogen receptor positivity and subjective dry-eye symptoms, tear break-up time, or Schirmer I and II test results. There was no difference in the proportion of cells expressing estrogen receptors between female and male patients (P=0.5).ConclusionsThe amount of meibomian gland cells expressing estrogen receptors in the lower lid seems to increase with age independent of gender and seems not to affect the fat layer and stability of the tear film.

Feasibility of intravitreal erythropoietin injections in humans

Background/aims: Preclinical data suggest that intravitreally administered erythropoietin (EPO) is both neuroprotective and safe. In a small pilot series, we intended to assess the feasibility of intravitreal EPO injections in humans. Methods: Three patients with acute vascular occlusion of the posterior pole received a single intravitreal EPO injection of 2000 U. Immediately before the injection and over the ensuing 3 months, these patients were closely monitored by measuring visual acuity, visual fields, intraocular pressure, the electroretinogram, the haematocrit and serum EPO levels. Results: Over the observational period, most parameters remained unchanged except for a short-term rise of serum EPO levels, which, however, did not exceeded normal serum levels. No injection-related toxicity was observed. Conclusion: Based on this limited set of data, a single EPO injection of 2000 U, a dose adapted from previous in vivo studies, is feasible and seems to induce no obvious damage. Hence, further investigations of this therapeutic approach appear justified.

Levels of VEGF but not VEGF165b are Increased in the Vitreous of Patients With Retinal Vein Occlusion

PURPOSE To determine the concentration of the pro-angiogenic vascular endothelial growth factor VEGF(165) (VEGF) and the anti-angiogenic VEGF(165b) in vitreous samples of patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in comparison to patients without retinal occlusive disease. DESIGN Experimental laboratory investigation. METHODS Vitreous samples were collected from patients undergoing surgery for arteriovenous dissection after BRVO, radial optic neurotomy after CRVO in the occlusion group, or macular pucker or macular hole in the control group. Concentrations of VEGF and VEGF(165b) were determined by ELISA and an ELISA-type antibody microarray. RESULTS Average vitreal concentration of VEGF was 8.6 ng/mL in the CRVO group and 2.0 ng/mL in the BRVO group as compared to 0.26 ng/mL in the control group. Average vitreal concentration of VEGF(165b) was 27 pg/mL in the CRVO group, 42 pg/mL in the BRVO group, and 49 pg/mL in the control group. In patients with CRVO and BRVO, the angiogenic balance was shifted towards angiogenic stimulation. CONCLUSION The severity of RVO from BRVO to CRVO correlates with an increase of VEGF and the decrease of VEGF(165b), indicating a pro-angiogenic shift. Altering the ratio of VEGF(165b)/VEGF(165) might be a feasible approach for treating retinal occlusive diseases.

Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis

BackgroundChoroidal neovascularisation (CNV) as a feature of exudative age-related macular degeneration (AMD) is partially regulated by retinal pigment epithelium (RPE). In this study, the effect of combinatory anti-angiogenic treatment was evaluated using a novel in vitro assay of RPE-induced angiogenesis.MethodsRPE isolated from surgically excised CNV-membranes (CNV-RPE) was used to stimulate sprouting of endothelial cell (EC) spheroids in a 3D collagen matrix. The anti-angiogenic effect of solitary anti-VEGF antibodies (bevacizumab) was compared to a combinatory treatment with anti-VEGF and anti-FGF2 antibodies.ResultsAnti-VEGF treatment inactivated all RPE-derived VEGF but was unable to fully inhibit EC sprouting induced by CNV-RPE. Combined anti-VEGF/anti-FGF treatment inactivated both growth factors and reduced EC sprouting significantly. ConclusionsRPE from CNV patients expresses angiogenic growth factors that act in part independently of VEGF. Targeted combinatory therapy can be superior to solitary anti-VEGF therapy. One possible candidate for combinatory therapy is FGF2.

Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema.

Purpose: This study compares vitreal levels of erythropoietin (EPO) in patients with retinal vein occlusion (RVO) with control subjects. In addition, it investigates different RVO disease parameters (time of vein occlusion, patient age, vitreal vascular endothelial growth factor (VEGF) levels, and extent of central macular edema) for possible correlations with vitreal EPO levels. Methods: Serum and vitreal EPO were measured from 6 patients with branch retinal vein occlusion, 6 patients with central retinal vein occlusion, and 12 control subjects (10 macular puckers and 2 macular holes). Results: Serum EPO levels (9.8 ± 4.9 mU/mL) did not differ between the RVO and control groups and were significantly lower than vitreal EPO levels in all groups. Vitreal EPO was elevated both in branch RVO (91 ± 59 mU/mL) and central RVO (182 ± 70 mU/mL) compared with controls (35 ± 24 mU/mL). Increased vitreal EPO correlated with higher vitreal VEGF (r = 0.64, P = 0.0008) and more pronounced central macular edema (r = 0.66, P = 0.001). Conclusion: The results from this study indicate that EPO is locally expressed in the retina and that it is upregulated together with VEGF in RVO eyes. Because of its role both in neuroprotection and angiogenesis, ocular EPO might represent an interesting target to investigate in patients with RVO, especially in light of the current anti-VEGF treatments.