Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease-a multicenter, retrospective analysis.

PURPOSE: To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT). METHODS: Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer's test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy. RESULTS: Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% (n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% (n = 32) NIH 2 and 39% (n = 41) NIH 3. The mean BCVA improved in 82% of the eyes (n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen's effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027-0.141) with each increase of corneal staining by one grade (p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% (n = 44) of the eyes. Postoperative complications included corneal perforation (n = 6, 6%), cystoid macular edema (n = 4, 4%), and endophthalmitis (n = 1, 1%). CONCLUSION: Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations.

Quality Assurance in Cataract and Lens Surgery with Special Consideration of Subjective Patient Reported Outcome Measures and Clinical Reported Outcome Measures. / Qualitätssicherungen in der Katarakt- und Linsenchirurgie unter besonderer Berücksichtigung der subjektiven Patientenbeurteilung und der refraktiven Ergebnisse.

BACKGROUND: Results of medical interventions must be documented and evaluated. In studies, this is done with clinical outcomes data (clinician/clinical reported outcome measure, CROM). In the past, less weight has been given to patient surveys with questionnaires (patient reported outcome measure, PROM). PATIENTS/MATERIALS AND METHODS: This retrospective study included 104 eyes from 53 patients. Of these, 35 patients had cataract surgery and 15 patients had a refractive lens exchange. The implanted lenses included 62 trifocal IOLs (Asphina trifiocal 839, Zeiss), 34 trifocal toric IOLs (Asphina trifocal toric 939, Zeiss) and 8 bifocal IOLs (Asphina 808, Zeiss) with the same IOL platform. Patients completed a modified questionnaire before surgery and one year after surgery. We made changes to the CatQuest-9SF questionnaire so as to also document side effects. RESULTS: The effort required by the patients to answer the questionnaire was a burden. Transcribing the data into electronic files so as they could be saved and analyzed was a lot of work for the staff. Among the patients, 88.7% were spectacle-independent in everyday life, and 77.5% for reading. 44.4% had a halo problem. 92% reported the operation as a success. 100% had a prediction error of ≤ ± 0.75 dpt. CONCLUSION: There is a high rate of patient satisfaction with the outcome of the intervention. New questionnaires are needed for new IOLs. The Catquest-9SF is from 2009. Accordingly, revisions and new validation is necessary. Beyond that, only automatic data transfer will reduce the amount of work involved in data input.

Semifluorinated Alkane Eye Drops in Chronic Ocular Graft-versus-Host Disease: A Prospective, Multicenter, Noninterventional Study.

PURPOSE: Ocular graft-versus-host disease (oGvHD) following allogeneic hematopoietic stem cell transplantation develops as severe dry eye disease (DED) and is initially treated with lubricants, although no clinical trials are available using artificial tears in oGvHD. This trial was set up to test perfluorohexyloctane (NovaTears®) as nonpreserved layer-forming agent for the treatment of DED in oGvHD. METHODS: 25 patients with severe DED due to oGvHD received 1 drop perfluorohexyloctane 4 times daily during a prospective, multicenter, observational 12-week study on top of established topical therapy. Clinical parameters included Schirmer test, tear film breakup time, corneal staining, meibum secretion and ocular surface disease index. Adverse events, visual acuity and intraocular pressure were key safety parameters. RESULTS: From 25 patients recruited, 23 presented for the second visit. Perfluorohexyloctane treatment did not lead to any changes in clinical or safety parameters but led to fast relief in symptoms in 57% of the patients. One adverse reaction occurred. CONCLUSIONS: This study showed no change in clinical signs in severe DED due to oGvHD, which was not unexpected due to the underlying pathomechanisms. However, the study showed improvement of symptoms in individual patients allowing application of perfluorohexyloctane as an additional symptomatic therapy in oGvHD.

Graft dislocation and graft failure following Descemet membrane endothelial keratoplasty (DMEK) using precut tissue: a retrospective cohort study.

PURPOSE: Although the functional results following DMEK are better than after DSAEK, DSAEK still seems to be the standard procedure, as surgeons fear losing grafts during DMEK graft preparation. Therefore, eye banks offer precut DMEK grafts for direct use by the surgeon. Here, we analysed the functional results and complication rates for a precut technique compared to fresh preparations. METHODS: We retrospectively compared 453 standard to 11 precut (1-2 days before surgery) DMEK cases. Precut preparations did not differ from the standard preparation, except that the preparation was stopped after trephination with the graft still attached in a small central area. The preparation had to be completed before surgery by peeling off the centrally attached part of the graft. This technique was first tested in an experimental series of 14 grafts, which were unsuitable for transplantation. All surgeries were performed in the same standardized way. RESULTS: There was no significant endothelial cell loss during the storage period following precut preparation. We found a statistically significantly higher endothelial cell loss and graft failure rate for the precut grafts. CONCLUSION: Because of the statistically significant higher graft failure rate in the precut group, we stopped using this technique, so the numbers in this retrospective case series are small. The higher graft failure rate may be explained by (ultra)structural changes in the DMEK graft (e.g. accumulation of dextran) during the second storage period. Therefore, careful evaluation is recommended before using precut DMEK grafts stored in dextran containing media in order to avoid early primary graft failures.

Descemet membrane endothelial keratoplasty for graft failure following penetrating keratoplasty.

PURPOSE: Descemet membrane endothelial keratoplasty (DMEK) is superior to penetrating keratoplasty (PK) in terms of visual rehabilitation, intraoperative safety and risk of rejection. Therefore, it seems reasonable to perform DMEK in eyes with endothelial failure following PK. We herein report our first clinical results. METHODS: Nineteen eyes with endothelial graft failure following PK were treated with DMEK. The majority of these eyes (12) had limited visual potential. The major indication for DMEK was pain relief in patients with bullous keratopathy. Visual acuity (VA), central corneal thickness (CCT), rate of graft dislocations, graft survival, graft rejections and other complications were extracted from the medical records. RESULTS: Although comorbidities limiting VA were present in 12 of the 19 eyes, VA increased from 0.05 to 0.1 (median) in 16 eyes. CCT decreased substantially (range 63-363 µm). Rebubbling was necessary in five eyes with incomplete graft adherence. There were two immunologic graft reactions and three graft failures. No major complications like endophthalmitis or expulsive bleeding occurred. CONCLUSIONS: DMEK is feasible to treat endothelial graft failure following PK. This is even true for eyes with limited visual potential.

Long-term follow-up after scleral lens fixation in patients with Marfan syndrome.

BACKGROUND: The dislocation of the crystalline lens is a common finding in patients with Marfan syndrome (MFS). Scleral intraocular lens (IOL) fixation is an accepted treatment method of this complication. To now, no long-term data on scleral IOL fixation in MFS exist. METHODS: We present a retrospective study of 27 eyes of 17 MFS patients that underwent scleral lens fixation at our clinic between 1999 and 2012. These patients are compared to an age- and surgeon-matched group of 31 eyes of 27 patients who underwent the same procedure for reasons other than MFS. RESULTS: The median age in the MFS group was 35.4 years versus 35.6 years in the non-MFS group. The median follow-up was 4 years for MFS and 3 years for non-MFS. In the MFS group, significantly more IOL-dislocations occurred than compared to the non-MFS group (30% vs. 6.5%, p = 0.02). Retinal detachment occurred in four MFS-eyes compared to three eyes in the non-MFS group. Biometry prediction error was 1.11 diopters (D) for MFS and 1.33 D for non-MFS (p = 0.11). Median BCVA (best-corrected visual acuity, logMAR) was 0.1 in the MFS group versus 0.3 in non-MFS patients. CONCLUSION: Scleral lens fixation in MFS patients achieves satisfying visual and refractive outcomes. Our data shows a significantly higher rate of IOL dislocations in patients with MFS. We therefore recommend addressing this complication preoperatively.

Modulation of focal adhesion constituents and their down-stream events by EGF: On the cross-talk of integrins and growth factor receptors.

Within the concept of integrin growth factor receptor (GFR) cross-talk, little is known about the effects of GFRs on focal adhesions (FAs). Therefore, we tested the hypothesis whether EGF can modulate constituents of FAs and subsequent down-stream events. To this end, EGF-treated keratinocytes were subjected to combined fluorescence imaging and western blotting, to quantify expression and/or activation of molecules, involved in integrin GFR cross-talk, and receptor proximal and distal signaling events. Generally, EGF response revealed an amplified redistribution or activation of molecules under study, which will be explained in detail from the plasma membrane to the cell interior. In addition to significant activation of EGF receptor (EGFR) at tyrosine Tyr845, a remarkable redistribution was detectable for the focal adhesion constituents, integrin ß1 and ß3, and zyxin. Increased activation also applied to focal adhesion kinase (FAK) by phosphorylation at Tyr397, Tyr576, and Src at Tyr418, while total FAK remained unchanged. Risen activity was seen as well for the analyzed distal down-stream events, p190RhoGAP and MAP kinases p42/44. Intriguingly, Src-specific inhibitor Herbimycin A abrogated the entire EGF response except FAK Tyr397 phosphorylation, independent of EGF presence. Mechanistically, our results show that EGF modulates adhesion in a dual fashion, by firstly redistributing focal adhesion constituents to adhesion sites, but also by amplifying levels of activated RhoA antagonist p190RhoGAP, important for cell motility. Further, the findings suggest that the observed EGF response underlies an EGFR integrin cross-talk under recruitment of receptor proximal FAK and Src, and MAP kinase and p190RhoGAP as receptor distal events.

Concise reviews: the role of biomechanics in the limbal stem cell niche: new insights for our understanding of this structure.

The limbal stem cell niche is a structure of the ocular surface that is characterized by high specification, organization, and clinical significance. Harboring the limbal epithelial stem cells, which are the progenitor cells of the corneal epithelium, it provides a niche environment that guarantees the self-renewal of the corneal epithelial stem cells throughout life. Growth factors, stromal niche cells, and specific extracellular matrix compositions provide this environment. In recent years, another important component has been added to this list: the biomechanical aspect of the niche. This review focuses on this new and still underestimated aspect, which exhibits a direct effect on cells and can also influence growth and differentiation.

Substrate elasticity as biomechanical modulator of tissue homeostatic parameters in corneal keratinocytes.

This study aimed at identifying putative modulations of tissue homeostatic parameters in corneal keratinocytes in response to biomechanical cues as basis for innovative cornea biomechanical-tailored biomaterials. Since cornea epithelial biomechanics is already described for contacts on nanostructures, we herein analyzed cell response to mechanical substrate elasticity. Therefore, corneal keratinocytes were established on physiologically-relevant elastic substrates of 40kPa, 130kPa but also on non-physiological stiff substrates of 1.74MPa for 3 days. qPCR revealed that changes in gene expression were only marginal between 40kPa and 130kPa, while significant modulations were seen on 1.74MPa substrates for most tissue-innate biomarkers under study. Gene expression fairly coincided with the protein, with differentiation progression biomarkers involucrin and fillagrin being already significantly increased between elasticities of 40kPa and 130kPa. Regarding focal adhesions, reinforcement was seen for ß1 integrin and phospho- p(125FAK) between 40kPa and 130kPa, while from 130kPa to 1.74MPa actin redistributed and phospho-p(125FAK) was strikingly up-regulated. These findings suggest elasticity dependence for differentiation progression and focal adhesion dynamics of corneal keratinocytes, supporting the concept of biomechanics governed regulation of tissue homeostasis. Moreover, this concept in turn can be translated into prospective cornea-tailored biomaterials for therapeutic approaches in ophthalmology.

Generation and evaluation of a human corneal model cell system for ophthalmologic issues using the HPV16 E6/E7 oncogenes as uniform immortalization platform.

The present study aimed at employing the human papillomavirus type 16 (HPV16) E6/E7 gene platform, to create a uniform authentic in vitro model cell system of the human cornea for ophthalmologic issues and here especially for prospective biomaterial evaluations for therapeutic regenerative approaches. Therefore, HPV16 E6/E7 genes were employed as uniform platform to immortalize primary human corneal keratinocytes (IHCK), fibroblasts (IHCF), and endothelial (IHCE) cells. qPCR revealed that E6/E7 mRNA transcription persisted at rising passages and FISH detection of the chromosome portfolio 1, 8, 10 and 18 showed fairly the disomic cytogenetic status. Hot spot passages proved oscillation of aneuploidies in the entire passage spectrum under study, while hot spot aneuploidies annotated prevalence for distinct chromosomes. Though IIF revealed general endurance, tissue-innate corneal biomarkers were modulated, i.e. expressed in a temporal-confluence, temporal-spatial or passage-dependent manner. In summary, by the fairly normal chromosomal status, and expression of tissue-innate biomarkers, we created for the first time a uniform authentic in vitro model cell system of the human cornea, by application of the HPV16 E6/E7 immortalization platform only. This system renders a precious tool for prospective iterative in vitro studies on issues such as corneal tissue homeostasis, pharmaceutical generics, and/or evaluation of new biomaterials for clinical corneal applications.

Conjunctival HLA-DR and CD8 expression detected by impression cytology in ocular graft versus host disease.

PURPOSE: To assess the expression of human leucocyte antigen (HLA)-DR in epithelial cells and cluster of differentiation (CD8)-positive lymphocytes as possible markers of chronic ocular graft versus host disease (cGvHD) after hematological stem cell transplantation (HSCT). METHODS: Twenty-seven consecutive patients with dry-eye symptoms following HSCT (24 [89%] with peripheral blood stem cell transplantation and 3 [11%] with bone marrow transplants; 17 [63%] familiar allogenic grafts) and 19 age-matched controls were included. Conjunctival impression cytology specimens were stained for HLA-DR, cytokeratin 19, and CD8. Oxford grading scale, blinking frequency, Schirmer test, tear film break-up time (TBUT), and Ocular Surface Disease Index (OSDI) were also recorded. Wilcoxon nonparametric testing was used to compare controls and HSCT recipients and to assess HSCT recipient subgroups with and without clinical cGVHD. RESULTS: Eighteen patients showed clinical signs of ocular cGVHD. TBUT and Schirmer test scores were significantly lower in patients, while Oxford grades and OSDI were significantly higher than in controls. Epithelial HLA-DR expression was generally higher in HSCT recipients than in controls, but it did not correlate with ocular cGVHD status. CD8-positive lymphocytes were identified in five patients with ocular cGvHD and one control. CONCLUSIONS: A strong HLA-DR expression as detected by impression cytology appears to indicate a general HSCT response and fails to predict ocular cGVHD. However, the detection of CD8-positive lymphocytes using impression cytology was frequently associated with ocular cGvHD. Our data warrant further evaluation of CD8 expression in impression cytology, along with comparison to conjunctival biopsies and brush cytology, as impression cytology may offer a less invasive strategy for assessing cGVHD status.

Cataract Surgery-Indications, Techniques, and Intraocular Lens Selection.

BACKGROUND: Opacification of the lens of the eye (cataract) is usually due to aging. It is a painless, progressive condition that affects contrast and color perception and alters refraction, leading to visual loss that may be total. In cataract surgery, the turbid lens is replaced by an artificial lens. An estimated 600 000 to 800 000 such procedures are performed in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including meta-analyses, Cochrane reviews, and randomized controlled clinical trials (RCTs). RESULTS: Cataract is the most common reversible cause of blindness around the world (approximately 95 million people). The surgical replacement of a turbid lens with an artificial lens is usually carried out under local anesthesia. The standard technique for fragmentation of the nucleus of the lens is ultrasonic phacoemulsification. RCTs have not shown the superiority of the femtosecond laser over phacoemulsification for this purpose so far. The spectrum of artificial intraocular lenses, aside from the conventional type with a single focus, include lenses with multiple foci, extended-depth-of-focus (EDOF) lenses, and astigmatism-correcting lenses. CONCLUSION: In Germany, cataract surgery is usually performed on an outpatient basis under local anesthesia. Artificial lenses with various additional functions are available nowadays; the choice of lens depends on the needs of the individual patient. Patients must be adequately informed about the advantages and disadvantages of the different lens systems.

Characterization of the Immediate and Delayed Biomechanical Response to UV-A Crosslinking of Human Corneas.

PURPOSE: Keratoconus leads to visual deterioration due to irregular astigmatism and corneal thinning. Riboflavin-based corneal UV-A crosslinking (CXL) induces novel intramolecular and intermolecular links resulting in corneal tissue stiffening, thereby halting disease progression. The purpose of this study was to analyze the immediate and delayed biomechanical responses of human donor corneas to CXL. METHODS: CXL was performed according to the Dresden protocol to corneas not suitable for transplantation. Biomechanical properties were subsequently monitored by measuring the Young modulus using nanoindentation. The immediate tissue response was determined after 0, 1, 15, and 30 minutes of irradiation. Delayed biomechanical effects were investigated with follow-up measurements immediately and 1, 3, and 7 days after CXL. RESULTS: Young's modulus indicated a linear trend in direct response to increasing irradiation times (mean values: total 61.31 kPa [SD 25.53], 0 minutes 48.82 kPa [SD 19.73], 1 minute 53.44 kPa [SD 25.95], 15 minutes 63.56 kPa [SD 20.99], and 30 minutes 76.76 kPa [SD 24.92]). The linear mixed model for the elastic response of corneal tissue was 49.82 kPa + (0.91 kPa/min × time [minutes]); P < 0.001. The follow-up measurements showed no significant delayed changes in the Young modulus (mean values: total 55,28 kPa [SD 15.95], immediately after CXL 56,83 kPa [SD 18.74], day 1 50.28 kPa [SD 14.15], day 3 57.08 kPa [SD 14.98], and day 7 56.83 kPa [SD 15.07]). CONCLUSIONS: This study suggests a linear increase of corneal Young modulus as a function of CXL timing. No significant short-term delayed biomechanical changes posttreatment were observed.

Low-dose AtropIne for Myopia Control in Children (AIM): protocol for a randomised, controlled, double-blind, multicentre, clinical trial with two parallel arms.

INTRODUCTION: Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. METHODS AND ANALYSIS: AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of -1 D to -6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. ETHICS AND DISSEMINATION: AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03865160.

Allogenic limbo-keratoplasty with conjunctivoplasty, mitomycin C, and amniotic membrane for bilateral limbal stem cell deficiency.

OBJECTIVE: To present the technique and report the results of up to 36 months after allogenic central penetrating limbo-keratoplasty in conjunction with conjunctivoplasty, mitomycin C (MMC), and amniotic membrane (AM) transplantation in patients with bilateral limbal stem cell deficiency (LSCD). DESIGN: Retrospective, consecutive subject cohort study. PARTICIPANTS: Case records of 20 eyes from 20 patients who presented with bilateral LSCD due to aniridia, chemical/thermal burn, cicatrizing pemphigoid, and chronic ocular surface inflammation and who were treated at the University Eye Hospital, Freiburg. METHODS: All eyes were treated with central limbo-keratoplasty in conjunction with conjunctivoplasty, MMC, and AM. There were 20 human leukocyte antigen-typed allolimbal transplants from cadaveric donors. All patients received systemic immunosuppression with mycophenolate mofetil or cyclosporine A. MAIN OUTCOME MEASURES: Surgical success was measured by the duration for which a healthy corneal epithelium was maintained. Visual success was measured by an improvement in visual acuity (VA) in the eye during follow-up and directly correlated with central clear graft survival. RESULTS: The follow-up period was up to 34 months (mean, 20 months; median, 22.4 months). Mean VA, measured in decimal fractions, increased from 0.029 (∼20/400; median, 0.005; first quartile 0.005; third quartile 0.005) before surgery to 0.281 (20/70; median, 0.2; first quartile 0.04; third quartile 0.55) after surgery. Healthy corneal epithelium showing survival of limbal stem cells was observed in 14 eyes (70%) during complete follow-up. CONCLUSIONS: Penetrating limbo-keratoplasty with conjunctivoplasty, MMC, and AM transplantation is a promising new surgical technique for improving vision and conjunctivalization in patients with severe bilateral LSCD necessitating allogenic transplants.

[Back-calculation of the keratometer index-Which value would have been correct in cataract surgery?] / Rückrechnung des Keratometerindex ­ Welcher Wert wäre bei der Kataraktchirurgie richtig gewesen?

BACKGROUND AND PURPOSE: In the clinical routine the conversion of corneal radii into corneal refractive power using a keratometer index is rarely discussed. The purpose of this study was to back-calculate the keratometer index in pseudophakic eyes based on the refractive power of the lens, biometric measurements and refraction, and to compare it to clinically established values. PATIENTS AND METHODS: In this retrospective case series 99 eyes of 99 patients without pathological alterations, previous diseases, comorbidities or history of ocular surgery apart from the uneventful cataract surgery were enrolled. In all eyes a CT Asphina 409M(P) (Carl-Zeiss Meditec, Berlin, Germany) had been implanted by two surgeons (EF and PE). For calculation we used shape and power data of the intraocular lens and data from optical biometry (axial length, pseudophakic anterior chamber depth, lens thickness, corneal radius; IOLMaster 700, Carl-Zeiss Meditec, Jena, Germany). The refraction was derived manually with a trial frame (measurement distance 5 m) and autorefractometry (iProfiler, Carl-Zeiss, Jena, Germany). For this three model eyes were used: a thin lens with the nominal refractive power positioned in the equatorial plane (model A) or in the secondary principal plane of the thick lens (model B) as well as a model considering the intraocular lens as a thick lens located at its measured position (model C). RESULTS: Back-calculation of the keratometer index using vergence formulas resulted in a keratometer index based on subjective refraction measurements considering lane distance correction of 1.3307 ± 0.0026/1.3312 ± 0.0026/1.332 ± 0.0027 for model A/model B/model C, respectively. Based on objective refraction measurements (autorefraction calibrated to infinity object distances) resulted in a keratometer index of 1.3301 ± 0.0021/1.3306 ± 0.0021/1.3315 ± 0.0021, for model A/model B/model C, respectively. The keratometer index did not show any trend in linear regression for axial length or corneal radius for any of the three models or for any refraction method. CONCLUSION: The keratometer index derived from back-calculation matched with the Zeiss index (1.332) but was much lower compared to other established indexes, e.g. the Javal index (1.3375). The missing trend for axial length or corneal radius implies that simple vergence formulas for intraocular lens refractive power calculation without correction terms or fudge factors perform best with a keratometer index slightly below 1.332, if the biometrically measured position of the intraocular lens is used as the effective lens position.

A corneal dystrophy associated with transforming growth factor beta-induced Gly623Asp mutation an amyloidogenic phenotype.

PURPOSE: To present the light and electron microscopic findings of a unique corneal dystrophy never before described in a German family carrying the Gly623Asp Mutation of the TGFBI gene with late clinical onset. DESIGN: Experimental study. PARTICIPANTS: Four affected and 6 nonaffected family members. METHODS: Slit-lamp examination, photographic documentation, and isolation of genomic DNA from peripheral blood leucocytes obtained from each family member examined. Exons 3, 4, 5, and 11 to 14 of the TGFBI gene were amplified and sequenced in these family members. Five corneal buttons of 3 affected siblings were excised at the time of penetrating keratoplasty. Light and electron microscopic examination were performed including immunohistochemistry with antibodies against keratoepithelin (KE) 2 and 15. MAIN OUTCOME MEASURES: Clinical and histologic characteristics of corneal opacification in affected patients and presence of coding region changes in the TGFBI gene. RESULTS: The specimens showed destructive changes in Bowman's layer and the adjacent stroma. Patchy Congo red-positive amyloid deposits were found within the epithelium in 1 cornea, in Bowman's layer and in the anterior stroma of all specimens also showing KE2, but not KE15, immunostaining. Electron microscopy revealed deposits mainly located in the anterior stroma and Bowman's layer and in small amounts in the basal area of some epithelial cells. The destroyed areas were strongly Alcian blue-positive, the Masson Trichrome stain proved mainly negative for the deposits. All affected but none of the unaffected family members had a heterozygous missense mutation in exon 14 of the TGFBI gene (G-->A transition at nucleotide 1915) replacing glycin by aspartic acid amino acid (Gly623Asp) at position 623 of the KE protein. CONCLUSIONS: In contrast with the patient carrying the Gly623Asp mutation of the TGFBI gene described by Afshari et al, our cases presented with Salzmann's nodular degeneration-like clinical features and their specimens contained KE2-positive amyloid. The reason for this now "meeting the expectation histologic phenotype" is unclear. The histologic findings emphasize that this is a unique corneal dystrophy, which shares no clinical characteristics with Reis-Bücklers' dystrophy and should be treated as a distinct entity. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.