UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial.

BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the "windscreen" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient's cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide. METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints). DISCUSSION: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

Ocular Involvement in Graft-versus-Host Disease. / Augenbeteiligung bei Graft-versus-Host-Erkrankung.

In ocular graft-versus-host disease (GVHD), an inflammatory reaction occurs at the ocular surface after transplantation of allogeneic hematopoietic stem cells. Self-reactive T cells of the donor are particularly responsible for this. This can lead to a pronounced wetting disorder of the ocular surface, conjunctival hyperemia, and corneal ulceration up to perforation. The ocular GVHD is associated with a high degree of suffering, such as pain, photophobia, and reduction in visual acuity. This review provides an overview of typical ophthalmological findings, topical and systemic therapeutic approaches, and concomitant measures (e.g., scleral lenses, punctum plugs) and the appropriate management of complications.

Systematic Review and Meta-analysis: Outcomes After Descemet Membrane Endothelial Keratoplasty Versus Ultrathin Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To compare the efficacy and safety of ultrathin Descemet stripping (automated) endothelial keratoplasty (UT-DS(A)EK) versus Descemet membrane endothelial keratoplasty (DMEK) for the treatment of Fuchs endothelial dystrophy (FED) and bullous keratopathy (BK). DESIGN: Systematic review and meta-analysis. METHODS: Literature containing DMEK and UT-DSAEK were searched in the Cochrane Database of Systematic Reviews, PubMed, EMBASE, LILACS, and through manual reference searching. Studies were included that measured the outcome of interventions-including best corrected visual acuity (BCVA), endothelial cell density (ECD), and postoperative complications, especially graft detachment with the need of re-bubbling, graft rejection, graft failure, and postoperative elevated intraocular pressure (IOP)-in patients with FED and BK. Included outcomes were pooled as standardized mean differences (SMD) or risk ratios (RR) using random effects models. Inter-study heterogeneity was assessed using the Q-test and I2 statistic. RESULTS: Seven (of 163) studies met all the inclusion and exclusion criteria. Meta-analysis showed a significantly better BCVA 12 months postoperatively, but an increased re-bubbling rate in eyes after DMEK compared with eyes after UT-DS(A)EK (BCVA: SMD = 0.50 [95% CI 0.27-0.74] and re-bubbling rate: RR = 0.33 [95% CI 0.16-0.67]). All other parameters did not differ significantly between both interventions, although estimates were imprecise (graft failure: RR = 0.65 [95% CI 0.18-2.30], graft rejection: RR = 1.40 [95% CI 0.27-7.30], and postoperative intraocular pressure elevation: RR = 1.14 [95% CI 0.60-2.18]). Postoperative SMDs of ECD could not be evaluated due to significant heterogeneity between studies. CONCLUSIONS: Although the improvement in BCVA was higher after UT-DS(A)EK than after conventional DS(A)EK, the BCVA after DMEK was still superior. The complication rates were comparable for both procedures, except for the higher rate of re-bubbling after DMEK.

Effect of Anti-TNF Treatment on Mooren's Ulcer: A Case Series and Review of the Literature.

PURPOSE: To report the efficacy of systemic anti-TNF agents in Mooren's ulcer. DESIGN: Retrospective, consecutive case series. METHODS: We report on clinical characteristics and outcome of five patients with Mooren's ulcer with anti-TNF treatment. RESULTS: During a mean follow-up of 30 months, relief of symptoms and arrest of corneal melting were observed in all eyes. Systemic corticosteroid treatment could be discontinued or reduced to threshold levels. No patient experienced adverse effects on bDMARDs. CONCLUSIONS: Our results suggest that bDMARDs are effective in Mooren's ulcer unresponsive to conventional treatment. This is in line with accumulating evidence in the current literature. Therefore, more targeted immunomodulatory approaches might be an effective first-line therapy in the future.

Graft failure rate and complications after Descemet membrane endothelial keratoplasty in eyes with pre-existing glaucoma.

PURPOSE: To evaluate the outcome of Descemet Membrane Endothelial Keratoplasty (DMEK) in eyes with pre-existing glaucoma. DESIGN: In this retrospective, observational case series we included data of 150 consecutive DMEKs in eyes with pre-existing glaucoma of 150 patients after excluding data of the second treated eye of each patient and of re-DMEKs during follow-up. Cumulative incidences of IOP elevation (IOP > 21 mmHg or ≥ 10 mmHg increase in IOP from preoperative value), post-DMEK glaucoma (need of an additional intervention due to worsening of the IOP), graft rejection, and graft failure rate were analyzed using Kaplan-Meier survival analysis. COX regression analysis was used to evaluate independent risk factors. RESULTS: The 36-month cumulative incidence of IOP elevation was 53.5% [95 CI 43.5-63.5%] and of post-DMEK glaucoma 36.3% [95 CI 26.3-46.3%]. Graft rejection occurred with a 36-month cumulative incidence of 9.2% [CI 95% 2.3-16.1]. None of the analyzed risk factors increased the risk for the development of graft rejection. The 36-month cumulative incidence of graft failure was 16.6% [CI 95% 8.4-24.8]. Independent risk factors for graft failure were the indication for DMEK "status after graft failure" (n = 16) compared to Fuchs' dystrophy (n = 74) (p = 0.045, HR 8.511 [CI 95% 1.054-68.756]) and pre-existing filtrating surgery via glaucoma drainage device (GDD) (n = 10) compared to no surgery/iridectomy (n = 109) (p = 0.014, HR 6.273 [CI 95% 1.456-27.031]). CONCLUSION: The risks of postoperative complications (IOP elevation, post-DMEK glaucoma, graft rejection, and graft failure) in patients with pre-existing glaucoma are high. In particular, pre-existing filtrating surgery via GDD implantation-but not trabeculectomy-and DMEK after graft failure increase the risk of graft failure.

[Chronic Blepharitis]. / Chronische Blepharitis.

Blepharitis represents a frequent inflammatory condition of the lids including the lid margin, which can be apparent in adults and children. Chronic blepharitis is therapeutically challenging. According to the anatomic localization, blepharitis can be graded in anterior and posterior forms. Blepharitis can lead to severe symptoms and complications, mainly dry eye disease, corneal complications and defective lid position. The pathogenesis of chronic blepharitis is not fully understood so far, however, multifactorial disease proceedings are supposed, which include systemic diseases (mainly dermatological disorders), habitual bacteria and infections. In all these processes inflammatory changes are the common final path.Therapeutic strategies include topical and systemic therapies, however evidence levels are generally low and patients are often resistant to therapy. Basic therapeutic measures are warm compresses, lid hygiene and lubricants. Topical anti-inflammatory drugs comprise corticosteroids and ciclosporin A. Topical and systemic antibiotics are commonly used. Systemic intake of omega-3 fatty acids is often recommended due to its anti-inflammatory potential.

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.

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.

Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

Survey of Rejection Prophylaxis Following Suture Removal in Penetrating Keratoplasty in Germany. / Umfrage zur Abstoßungsprophylaxe bei Fadenentfernung nach perforierender Keratoplastik in Deutschland.

BACKGROUND: Penetrating keratoplasty (PK) gets more and more reserved to cases of increasing complexity. In such cases, ocular comorbidities may limit graft survival following PK. A major cause for graft failure is endothelial graft rejection. Suture removal is a known risk factor for graft rejection. Nevertheless, there is no evidence-based regimen for rejection prophylaxis following suture removal. Therefore, a survey of rejection prophylaxis was conducted at 7 German keratoplasty centres. OBJECTIVE: The aim of the study was documentation of the variability of medicinal aftercare following suture removal in Germany. METHODS: Seven German keratoplasty centres with the highest numbers for PK were selected. The centres were sent a survey consisting of half-open questions. The centres performed a mean of 140 PK in 2018. The return rate was 100%. The findings were tabulated. RESULTS: All centres perform a double-running cross-stitch suture for standard PK, as well as a treatment for rejection prophylaxis with topical steroids after suture removal. There are differences in intensity (1 - 5 times daily) and tapering (2 - 20 weeks) of the topical steroids following suture removal. Two centres additionally use systemic steroids for a few days. DISCUSSION: Rejection prophylaxis following PK is currently poorly standardised and not evidence-based. All included centres perform medical aftercare following suture removal. It is assumed that different treatment strategies show different cost-benefit ratios. In the face of the diversity, a systematic analysis is required to develop an optimised regimen for all patients.

Recovery of Contrast Sensitivity After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To study the change in contrast sensitivities in eyes with Fuchs endothelial dystrophy and bullous keratopathy after Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this prospective study, 50 pseudophakic eyes of 50 patients who received DMEK surgery at the Charité-Universitätsmedizin Berlin were included. Visual acuity; contrast sensitivity using OPTEC 6500 at spatial frequencies of 1.5, 3, 6, 12, and 18 cycles/degree in photopic and mesopic light with and without glare; central corneal thickness (CCT); and anterior and posterior corneal aberrations were measured preoperatively and at 3 and 12 months postoperatively. RESULTS: Best-corrected visual acuity (preoperative 0.67 ± 0.46 and after 12 months 0.19 ± 0.16 LogMAR, P < 0.001) and photopic and mesopic contrast sensitivities with and without glare improved significantly, whereas CCT decreased significantly (preoperative 677 ± 114 µm, after 12 months 527 ± 29 µm, P < 0.001). Preoperative CCT correlates significantly with preoperative photopic contrast sensitivity (correlation coefficient -0.462, P = 0.002), and postoperative total anterior aberrations correlates with postoperative photopic contrast sensitivity (correlation coefficient -0.361, P = 0.006). CONCLUSIONS: Photopic and mesopic contrast sensitivities, especially with glare, are impaired in patients with Fuchs endothelial dystrophy and bullous keratopathy. The extent of the corneal thickening seems to mainly influence the contrast sensitivity preoperatively. DMEK surgery improves the contrast sensitivity significantly. However, higher postoperative anterior corneal aberrations limit the postoperative contrast sensitivities.

Impact of Re-bubbling after Descemet Membrane Endothelial Keratoplasty on Long-term Results.

Purpose/Aim of the study: Graft detachment after DMEK can be treated easily with an additional air injection - re-bubbling. The aim of our study was to investigate the effect of a re-bubbling on the postoperative outcome.Materials and Methods: In this retrospective, comparative, cohort study we included eyes from patients that underwent DMEK surgery. A graft detachment was diagnosed by slit-lamp examination and OCT scan. All eyes were divided into three groups: no re-bubbling, one re-bubbling, more than one re-bubbling. We analyzed the visual acuity, endothelial cell density and rate of graft failure.Results: In 163 of 463 eyes (35.2%) a re-bubbling was performed (119 eyes 1 re-bubbling, 44 eyes more than one re-bubbling). Visual acuity improved significantly in all groups. After controlling for donor age, reason for surgery, time of cultivation of the graft and preoperative visual acuity, no difference in the visual acuity was seen at any point of follow-up. All patients showed a significant reduction in endothelial cell density 1 month after DMEK. Controlling for donor age, reason for surgery, type of surgery (DMEK-only or DMEK combined with cataract surgery) and the time of cultivation of the graft, the difference in endothelial cell density at 1 month post-surgery between no re-bubbling and one re-bubbling was 157 cells/mm2 (95% CI 2-310, p = .047) and between no re-bubbling and more than one re-bubbling 504 cells/mm2 (95% CI 267 - 741, p < .001). The difference in endothelial cell density remained over the course of follow-up. Twenty patients (4.3%) developed a graft failure during postoperative follow-up. Controlling for donor age, reason for surgery and the time of cultivation of the graft, we did not find any difference in the risk of graft failure between re-bubbling categories.Conclusions: Re-bubbling increased the risk for an endothelial cell loss, but did not influence the postoperative visual acuity and the rate of graft failure.

Impact of difficult unfolding and attachment of the graft lamella on the long-term outcome after Descemet membrane endothelial keratoplasty.

PURPOSE: Unfolding and attachment of the posterior donor lamella may be the most challenging part in Descemet membrane endothelial keratoplasty (DMEK) procedure. We investigated the correlation of the difficulty degrees of this step to the postoperative clinical outcome 6 years after surgery. METHODS: One hundred sixty-nine consecutive DMEKs between September 2012 and August 2013 at the Charité-University Medicine Berlin were graded prospectively into 4 groups according to their grade of difficulty in unfolding and attachment of the graft lamella. Postoperative visual acuity, endothelial cell density, and rate of graft failure were measured after 1 year, after 2 years, and after 6 years and analyzed according to their grading group. RESULTS: Visual acuity improved significantly in all groups and did not differ significantly between the grading groups at any time point postoperatively. There was a significant decrease of endothelial cell density in all groups with a significantly higher endothelial cell loss in group IV compared with the other groups within the first 24 months after surgery. The graft failure rate was significantly higher in eyes graded III and IV than in groups I and II (p = 0.012). CONCLUSION: Although the endothelial cell loss and the graft failure rate increase significantly with a more difficult graft unfolding and attachment, DMEK surgery is a promising procedure with a good long-term postoperative outcome. A direct manipulation of the graft lamella for unfolding and centering by cannula or forceps should be avoided if possible to reduce the risk of an increased endothelial cell loss and a higher graft failure rate. TRIAL REGISTRATION: NCT02020044.

[Second Survey on Patient-centred Care of Ocular Graft-versus-Host Disease in Germany]. / Zweite Umfrage zur Versorgungsstruktur der okulären Graft-versus-Host Disease in Deutschland.

BACKGROUND: graft-versus-host disease (GvHD) is a common complication after allogeneic haematopoietic stem cell transplantation (allo-SCT) and causes immunological rejection of host tissues, which can occur both acute or chronically. Approximately 40 - 80% of patients with the diagnosis of chronic GvHD (cGvHD) also develop ocular GvHD. For these patients, immediate and uncomplicated access to interdisciplinary patient-centred care is important. We performed this survey to improve understanding of the structure of patient-centred care in Germany. METHODS: The GvHD working party of the Cornea Section of the German Society of Ophthalmology sent the "Survey of ocular GvHD 2016" to all university and specialised hospitals in Germany. We evaluated the data and compared the information with survey results from 2014, in order to draw conclusions about the structure and process of patient-centred care in ocular GvHD. Besides the questions from 2014 on the numbers of allo-SCT, frequency of examinations, etc. there were additional questions on the prescription of ciclosporin and autologous serum eye drops. The question on frequency examination was further expanded to include examinations of paediatric patients. RESULTS: Of 30 participating hospitals, 22 had already taken part in the first survey. According to the information they provided, approx. 1860 allo-SCTs were performed in the transplantation units of the participating eye hospitals in 2016. This was more than half of the transplantations performed in Germany. Ophthalmologists examined between 2 and 250 Patients per year per centre. Eight clinics provide a specialised outpatient clinic for ocular GvHD. Nearly all the participating clinics prescribe ciclosporin eye drops. About ⅔ provide autologous serum eye drops, seven obtain them from external sources. Overall approx. 125 - 140 children were examined in 2016. CONCLUSIONS: Due to the potential severity of ocular GvHD with immobilisation of the patients and the imminent loss of sight, further improvements in eye care are required. For example, offers such as special consultations, with expertise located close to any transplantation unit are recommended. This requires in particular ophthalmologists to participate in the patient care to enhance quality of life after allo-SCT. In summary, we conclude that the present structures are not sufficient to treat all patients suffering from ocular GvHD in Germany, but the situation has evidently improved.

[Neurotrophic keratopathy : Principles, diagnostics and treatment]. / Neurotrophe Keratopathie : Grundlagen, Diagnostik und Therapie.

Corneal nerves are responsible for the reception of pain, temperature, and touch and are an important component of homeostasis of the ocular surface. When the corneal innervation is reduced, degenerative changes can be manifested as neurotrophic keratopathy (NK). In a stage-dependent course, corneal epithelial alterations and ulcers may occur, even leading to perforation. The cause of NK is predominantly damage to the trigeminal nerve, which can be caused by infections (especially herpesviruses), metabolic diseases (such as diabetes mellitus) and by surgical procedures. The diagnosis of NK requires a detailed medical and ocular history, assessment of corneal sensitivity, and a complete ocular examination. The treatment of NK is oriented to the clinical severity and aims to restore the integrity of the ocular surface in order to prevent further disease progression.

Retrospective, controlled observational case study of patients with central retinal vein occlusion and initially low visual acuity treated with an intravitreal dexamethasone implant.

BACKGROUND: Patients with initially low visual acuity were excluded from the therapy approval studies for retinal vein occlusion. But up to 28 % of patients presenting with central retinal vein occlusion have a baseline BCVA of less than 34 ETDRS letters (0.1). The purpose of our study was to assess visual acuity and central retinal thickness in patients suffering from central retinal vein occlusion and low visual acuity (<0.1) in comparison to patients with visual acuity (≥0.1) treated with Dexamethasone implant 0.7 mg for macular edema. METHODS: Retrospective, controlled observational case study of 30 eyes with macular edema secondary to central retinal vein occlusion, which were treated with a dexamethasone implantation. Visual acuity, central retinal thickness and intraocular pressure were measured monthly. Analyses were performed separately for eyes with visual acuity <0.1 and ≥0.1. RESULTS: Two months post intervention, visual acuity improved only marginally from 0.05 to 0.07 (1 month; p = 0,065) and to 0.08 (2 months; p = 0,2) in patients with low visual acuity as compared to patients with visual acuity ≥0.1 with an improvement from 0.33 to 0.47 (1 month; p = 0,005) and to 0.49 (2 months; p = 0,003). The central retinal thickness, however, was reduced in both groups, falling from 694 to 344 µm (1 month; p = 0.003,) to 361 µm (2 months; p = 0,002) and to 415 µm (3 months; p = 0,004) in the low visual acuity group and from 634 to 315 µm (1 month; p < 0,001) and to 343 µm (2 months; p = 0,001) in the visual acuity group ≥0.1. Absence of visual acuity improvement was related to macular ischemia. CONCLUSIONS: In patients with central retinal vein occlusion and initially low visual acuity, a dexamethasone implantation can lead to an important reduction of central retinal thickness but may be of limited use to increase visual acuity.

Verification of the new grading scale for ocular chronic graft-versus-host disease developed by the German-Austrian-Swiss consensus conference on chronic GVHD.

The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications.

Recurrent episodes of night blindness in a patient with short bowel syndrome.

PURPOSE: To describe clinical characteristics in a patient with recurrent episodes of night blindness due to vitamin A deficiency caused by short bowel syndrome in Crohn disease. METHODS: Retrospective analysis of best-corrected visual acuity (BCVA), kinetic perimetry, slit-lamp biomicroscopy, ophthalmoscopy, fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT), dark adaptometry (DA) and electroretinography (ERG). Serum vitamin A level was measured. RESULTS: A 44-year-old man with a 3-year history of night blindness suffered from a short bowel syndrome with chronic malabsorption due to ileocecal resection in Crohn disease. Both eyes had a BCVA of 0.9, Bitot's spots of the conjunctiva and no significant fundus abnormalities. SD-OCT showed no remarkable changes, whereas FAF was brighter than normal in the center of the fovea. DA showed normal cone and a lack of rod function. The dark-adapted 0.01 ERG was non-detectable, the dark-adapted 3.0 ERG severely diminished, but the light-adapted 3.0 and 30 Hz flicker ERGs were within normal limits. Serum vitamin A level was 0.11 µg/ml (normal 0.30-0.65 µg/ml). Treatment with intravenous vitamin A caused a rapid recovery of night vision and ERG. However, during the following 3 years, he had three further episodes of night blindness with loss of rod function. During each period, parenteral vitamin A substitution brought complete recovery of night vision and rod function. BCVA, fundus, FAF findings and SD-OCT remained unchanged during the course. CONCLUSIONS: In patients with known chronic malabsorption serum vitamin A level should be regularly checked to avoid recurrent night blindness episodes. ERG might be more sensitive than serum vitamin A level and is recommended in case of night blindness but still normal vitamin A level.

Retinal Involvement in a Patient with Cerebral Manifestation of Chronic Graft-Versus-Host-Disease.

BACKGROUND: We report a 35-year-old female patient with cerebral manifestations of chronic graft-versus-host disease (cGvHD) and putative retinal involvement after allogeneic peripheral blood stem cell transplantation (alloHSCT). PATIENT AND METHODS: The patient experienced recurrent episodes of fever and encephalitic signs 7 months after alloHSCT during taper of immunosuppression (IS). RESULTS: Cerebral magnetic resonance imaging (MRI) showed non-gadolinium-enhancing confluent periventricular lesions and cerebrospinal fluid inflammation. After exclusion of infectious causes, treatment with steroids and antiepileptics improved cognitive deficits. Steroid reduction provoked a relapse responding to IS. 2 years later, she complained of right-sided blurred vision and floaters; both eyes showed whitish circumscribed retinal infiltrations, cellular infiltration of the vitreous and mild bilateral optic disc edema. Oncological and neurological work-up ruled out infectious diseases and other GvHD manifestations. Symptoms and signs resolved under continued systemic IS, leaving pigmented retinal scars. After IS withdrawal, classical cutaneous cGvHD developed, resolving on systemic IS. 94 months after transplantation, she is doing well. CONCLUSION: To our knowledge, this is the first observation of retinal involvement of cerebral cGvHD manifestations with retinal infiltrations documented in the absence of other causes and in parallel to periventricular lesions in cerebral MRI. Based on bone marrow histology, we discuss a small vessel pathophysiology of cGvHD.

Comparative analysis of the basement membrane composition of the human limbus epithelium and amniotic membrane epithelium.

PURPOSE: Human amniotic membrane has been widely used as substrate for ex vivo expansion and transplantation of limbal epithelial cells. To further clarify its suitability as a surrogate niche for limbal stem cells and progenitor cells, we analyzed the composition of the amniotic epithelial basement membrane, with special focus on the expression of limbus-specific matrix components. METHODS: Cryosections of corneoscleral specimens obtained from 10 human donor eyes and of 6 amniotic membrane specimens obtained at cesarean section were stained by indirect immunofluorescence using a broad panel of antibodies against basement membrane components. RESULTS: Both amniotic and limbal epithelial basement membranes showed positive immunoreactivity for collagen type IV α1, α2, α5, and α6 chains; collagens type VII, XV, XVI, XVII, and XVIII; laminin α3, ß1, ß2, ß3, γ1, and γ2 chains; laminin-111 and laminin-332; nidogen-1 and nidogen-2; fibronectin; fibulin-2; fibrillin-2; perlecan; and agrin. Both types of basement membrane were negative for collagen type IV α3 and α4 chains, collagen type V, and laminin α4 chain. Limbal basement membrane components, which were not detected in amniotic membrane, included laminin α1, α2, α5, and γ3 chains; BM40/SPARC; tenascin-C; matrilin-2; endostatin; and collagen type XVIII. CONCLUSIONS: Despite extensive similarities in basement membrane composition between amniotic and corneolimbal epithelia, the lack of limbus-specific environmental factors argues against the potential of denuded amniotic membrane as a surrogate niche for limbal stem cells but supports its suitability as a substrate to promote the formation of a well-differentiated stratified corneal epithelial equivalent for tissue engineering strategies.