Philip Maier

Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials

Abstract Objective Open angle glaucoma is one of the most common causes of blindness in industrialised nations. Treatments to lower ocular pressure are widely used in glaucoma prevention and treatment, despite conflicting evidence. Design We performed meta-analyses to reassess the effectiveness of pressure lowering treatment to delay the development of glaucoma in ocular hypertension, as well as progression of manifest open angle glaucoma. Data sources Medline, Embase, and the Cochrane Library. Selection of studies Eligible studies were randomised controlled trials with a concurrent untreated control group and information on time to glaucomatous changes to visual field and optic disc. Trial reports were reviewed independently by two investigators in an unblinded standardised manner. Results Meta-analysis of trials in ocular hypertension showed a significant preventive effect of reducing intraocular pressure on progression to glaucoma (hazard ratio 0.56, 95% confidence interval 0.39 to 0.81, P = 0.01; number needed to treat 12). Pooled data of studies in manifest glaucoma showed a significant delay of visual field deterioration (0.65, 0.49 to 0.87, P = 0.003; NNT = 7), with subgroup analysis showing a larger effect in patients with raised pressure and a reduced effect in normal tension glaucoma (subgroup comparison: not significant). Conclusions Lowering intraocular pressure in patients with ocular hypertension or manifest glaucoma is beneficial in reducing the risk of visual field loss in the long term.

Influence of donor characteristics on descemet membrane endothelial keratoplasty.

Purpose: Penetrating keratoplasty is being replaced by posterior lamellar techniques like Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of patients with endothelial insufficiency. Although DMEK leads to the best visual results, Descemet stripping automated endothelial keratoplasty is still the standard procedure for many surgeons because it is technically more standardized. Here, we investigated how donor characteristics may influence DMEK surgery. Methods: After in vitro preparation of DMEK grafts (n = 28), we measured the width of the graft roll, which we correlated to various donor characteristics. In 31 DMEK cases, we measured the intraoperative time from implantation to attachment of the graft, which we correlated to the respective donor characteristics and endothelial cell loss. We used Pearsons method and a multifactorial linear model for the statistical assessments. Results: We found a statistically significant correlation between donor age (P < 0.001) and endothelial cell density (P < 0.05), and the width of the DMEK rolls. That is, older donors and grafts with higher endothelial cell densities formed broader graft rolls. Donor age also showed a trend to directly influence the unfolding time that took longer using younger grafts. Furthermore, the relative endothelial cell loss increased with longer unfolding times. Conclusions: We found that donor age and endothelial cell density influence the properties of DMEK grafts, and thereby the duration of the surgical procedure. Increased unfolding times result in higher endothelial cell loss. Therefore, it seems reasonable to accept preferably older donors with high endothelial cell densities for DMEK, which may be particularly true for inexperienced surgeons or complex clinical situations.

[Corneal melting after cross-linking and deep lamellar keratoplasty in a keratoconus patient].

We present the case of a 45-year-old patient with severe atopic disease and keratoconus who suffered from corneal melting following cross-linking and deep anterior lamellar keratoplasty (DALK) due to subclinical infection with Herpes simplex virus (HSV). Penetrating keratoplasty and intensive antiviral and immunosuppressive medical treatment were necessary to control the infection. The case demonstrates the difficulties in the treatment of keratoconus in patients with severe atopic disease.

Long-term graft survival in penetrating keratoplasty: the biexponential model of chronic endothelial cell loss revisited.

Aim: To present a novel interpretation of the biexponential nature of chronic endothelial cell loss after penetrating keratoplasty (PK). We hypothesize that the fast component of endothelial cell loss reflects the endothelial cells of graft origin. The slow component might just reflect cell loss of the recipient endothelium. We investigate herein whether this hypothesis is in line with long-term survival in bullous keratopathy (BK: almost no endothelium in the recipient bed) and keratoconus (KK: recipient bed with plenty of endothelium). Methods: We reviewed endothelial graft failures in PK for BK (n = 88) and KK (n = 87). Patients with immune reactions or a history of glaucoma were excluded. We built a statistical model to predict graft failures from biexponential endothelial cell loss and compared this data to the actual outcomes. Results: After 15 years, the incidence of late endothelial failures was 8% in KK and 33% in BK. The 95% confidence intervals of the simulated outcomes corresponded completely to the actual outcomes during follow-up. Conclusions: Our novel interpretation of the biexponential model is in line with long-term data of PK for BK and KK. Our findings highlight the importance of the recipient bed endothelial reservoir on the long-term prognosis in PK.

Cystoid macular oedema following Descemet membrane endothelial keratoplasty

Background To determine the incidence and potential risk factors of cystoid macular oedema (CMO) following Descemet membrane endothelial keratoplasty (DMEK) with or without simultaneous cataract surgery. Methods In this study, 155 eyes of 88 patients suffering from Fuchs endothelial dystrophy (81%), bullous keratopathy (17.6%) or other corneal diseases (1.4%) underwent DMEK. 52% were pseudophacic (DMEK) and 48% received simultaneous cataract surgery (DMEK combined with cataract surgery (Triple-DMEK)) at the Eye Center at Albert Ludwigs University of Freiburg between May 2011 and June 2013. Spectral-domain optical coherence tomography (SD-OCT) was performed 6 weeks, 3 months and 6 months following (Triple-)DMEK and in unscheduled visits due to limited or decreased visual acuity. The medical records were reviewed for pre-existing comorbidities limiting visual acuity. Patients with a history of macular oedema were excluded. We estimated the incidence of CMO using the Kaplan–Meier method. Potential risk factors for CMO were analysed with a Cox regression analysis and Pearsons correlation. The Cox model included the following variables: patient age and axial length, simultaneous cataract surgery, rate of rebubbling, donor age and donor endothelial cell density. Results 13% of all eyes developed a single episode of CMO at the end of the follow-up. After 6 months, 13.3% of eyes following Triple-DMEK and 12.5% of eyes following DMEK showed CMO. There was a statistically significant correlation between CMO development and best spectacle corrected visual acuity. Long axial length had a protective effect on CMO development (HR=0.3; p=0.03). Under medical therapy, central foveal thickness decreased in all patients. CMO did not have a relevant effect on long-term visual acuity. Conclusions CMO is a frequent complication following DMEK in phacic and pseudophacic eyes. The prognosis is excellent given medical treatment. We recommend regular SD-OCT monitoring during the first 6 months following DMEK.

Clear graft survival and immune reactions following emergency keratoplasty

BackgroundEmergency penetrating keratoplasty is said to have a poorer outcome than conventional keratoplasty. We performed a retrospective analysis of 272 cases of emergency keratoplasty to evaluate this hypothesis.MethodsWe analysed 272 cases of emergency keratoplasty and compared the results with a control group of 1,257 scheduled normal-risk keratoplasties and 407 scheduled high-risk keratoplasties. Kaplan-Meier estimations were performed to estimate the percentage of clear graft survival and development of immune reactions. Indications for emergency keratoplasty were microbial diseases (n=109, acanthamoeba, bacteria, fungi), herpes simplex virus infections (n=83), ulcers due to immunological diseases (n=63), and 17 cases of ulcers of unknown origin.ResultsWithin 1,500 postoperative days, grafts following emergency keratoplasty suffered statistically significantly more graft failures (clear graft survival, 67.9 vs. 86.9%, P<0.01) and immune reactions (grafts free from immune reactions, 62.8 vs. 78.6%, P<0.01) than grafts following scheduled, normal-risk keratoplasty. There was no statistically significant difference between emergency and scheduled high-risk keratoplasties (clear graft survival, 67.9 vs. 70.2%, and grafts free from immune reactions, 62.8 vs. 66.8%). For emergency keratoplasties, systemic immunosuppression (with cyclosporin A and/or mycophenolatmophetil) had a statistically significant positive effect on clear graft survival (77.4 vs. 63.5%, P=0.01), but not on the development of immune reactions (62.8 vs. 62.3%). A sub-group analysis showed that the effect on clear graft survival was mainly an effect on the underlying systemic immunological disease that had lead to emergency keratoplasty.ConclusionThis retrospective analysis revealed that clear graft survival is limited following emergency keratoplasty. As in high-risk situations, systemic immunosuppression may be the key to improving prognosis following emergency keratoplasty in the long run.

The impact of corneal edema on intraocular pressure measurements using goldmann applanation tonometry, Tono-Pen XL, iCare, and ORA: an in vitro model.

Purpose:Among other corneal biomechanical properties, Goldmann applanation tonometry (GAT) has been shown to depend on corneal edema. New tonometry devices have been designed, such as the Tono-Pen XL, iCare, and ocular response analyzer (ORA), to measure the intraocular pressure (IOP) accurately. This study aims to investigate the influence of corneal edema on the accuracy of these IOP-measuring devices in an in vitro model. Methods:A model of an artificial anterior chamber was developed using a guided trephination system. Eight donor corneas not suitable for keratoplasty were clamped into this artificial anterior chamber. All corneas showed signs of stromal edema. Intracameral pressure (ICP) was adjusted manometrically to 10, 20, 30, 40, and 50 mm Hg. The central corneal thickness (CCT) was determined by ultrasonic pachymetry. For each manometrically defined ICP, tonometry was performed using the iCare, Tono-Pen XL, GAT, and ORA. Results:The mean CCT increased from 616.1±29.6 µm to 626.9±36.1 µm. At 10 mm Hg, GAT yielded a higher ICP than those manometrically adjusted (10.4±3.3 mm Hg); at all other ICP levels, GAT yielded lower ICP levels than those adjusted. The Tono-Pen XL and iCare showed the greatest difference at 10 mm Hg, with the Tono-Pen XL yielding a value of 14.0±4.0 mm Hg and the iCare yielding a value of 12.5±2.6 mm Hg. All other results of the 2 devices fell within a range of ±2 mm Hg from the adjusted ICP. The ORA provided accurate results only at “physiological” ICP levels with a maximum difference of 2.6 mm Hg at 30 mm Hg. At higher ICP levels, corneal hysteresis decreased significantly with increasing ICP. None of the measurement devices revealed a statistically relevant dependence on CCT in this experimental setting. Conclusions:The Tono-Pen XL and the iCare yielded the most accurate ICP values across all the adjusted ICP values. This may be because of their relatively small contact area with the cornea and, consequently, greater independence from corneal biomechanical properties. The ORA yielded accurate measurement results only at physiological ICP levels. As anticipated, GAT underestimated ICP. The Tono-Pen XL and the iCare should therefore be used to determine IOP in patients suffering from corneal edema, such as bullous keratopathy or Fuchs endothelial dystrophy.

Correlation between visual acuity and interface reflectivity measured by pentacam following DSAEK

Purpose:  Descemet‐stripping automated endothelial keratoplasty (DSAEK) is an advanced method of lamellar endothelial keratoplasty. In comparison with penetrating keratoplasty, visual rehabilitation seems to be faster. Final visual outcome of DSAEK, however, seems to be limited, especially in comparison with Descemet membrane endothelial keratoplasty (DMEK). DSAEK cases without graft failure often do not show any definite correlate for the reduced optical performance. In this study, we tried to correlate visual acuity following DSAEK with interface reflectivity as measured by a rotating Scheimpflug system.

Toxic Anterior Segment Syndrome Following Penetrating Keratoplasty

OBJECTIVES To describe an outbreak of toxic anterior segment syndrome (TASS) following penetrating keratoplasty (PK) and to examine its possible causes. METHODS Owing to a series of TASS following PK between June 6, 2007, and October 2, 2007, we reviewed the records of all patients who had undergone PK during that time. In addition to routine microbial tests on organ culture media, we looked for specific pathogens and endotoxins in all of the materials used for organ culture or PK. Furthermore, we analyzed all of the perioperative products and instrument processing. RESULTS Of the 94 patients who underwent PK, we observed 24 cases of postoperative sterile keratitis. Causal research revealed that the accumulation of cleaning substances or heat-stable endotoxins on the surface of the routinely used guided trephine system was most likely responsible for the TASS. CONCLUSIONS To our knowledge, this is the first report on TASS following PK. Suboptimal reprocessing of surgical instruments may be an important cause of TASS as in this series the TASS-like symptoms resolved after modified instrument-cleaning procedures. The standardization of protocols for processing reusable trephine systems might prevent outbreaks of TASS following PK.

Expression of p63 in conjunctival intraepithelial neoplasia and squamous cell carcinoma

Backgroundp63 is a homologue of the tumour suppressor gene p53, which is expressed in human basal squamous epithelium. Some investigators maintain that p63 plays a role in the development of squamous epithelium and, despite its homology to p53, it is considered to act as an oncogene. This study investigated the expression of p63 in conjunctival intraepithelial neoplasia of different grades, and conjunctival squamous cell carcinoma and its correlation to the proliferation marker MIB-1.Material and methodsSeventeen conjunctival specimens excised with the suspicion of either conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma were diagnosed histologically as follows: 2 squamous cell carcinomas of the conjunctiva, 2 CIN grade I, 3 CIN grade II, 7 CIN grade III, 2 CIN with beginning invasion and 1 normal conjunctiva with no dysplasia. Sixteen microscopically-normal postmortem conjunctival specimens and normal conjunctiva, CIN and carcinoma specimens were stained immunohistochemically with antibodies against p63 and MIB-1. At least 500 cells per specimen were counted and the percentage of positively-stained cells of each antibody was calculated.ResultsA mean of 80% (57–89%) of the dysplastic cells from the CIN specimens stained positively with antibodies against p63, especially in the lower two-thirds of the epithelium, statistically significantly more compared with the normal specimens (9–55%, mean 36%, p<0.001). Nevertheless, we did not find a correlation between the percentage of p63-positive cells and the differentiation grade of the malignant specimens. MIB-1 positivity was shown by 0–1% of the cells in the normal postmortem controls, by 3–30% (mean 12%) of the cells in the basal and occasionally in the middle layer of the CIN specimens, and 16–61% (mean 23%) in the carcinoma specimens.ConclusionIn conjunctival intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, p63 is preferentially expressed in the immature dysplastic epithelial cells. Its staining does not correlate with MIB-1-expression, and therefore does not appear to be linked to cell proliferation.