Franziska Bucher

Split Cornea Transplantation : Relationship between Storage Time of Split Donor Tissue and Outcome

PURPOSE To analyze the relationship between storage time of split donor tissue and outcomes after deep anterior lamellar keratoplasty (DALK) and Descemets membrane endothelial keratoplasty (DMEK). DESIGN Retrospective analysis of a nonrandomized, consecutive, interventional case series. PARTICIPANTS One hundred ten eyes with anterior stromal disease suitable for DALK and 110 eyes with endothelial disease suitable for DMEK underwent surgically successful split cornea transplantation combining both procedures within 7 days after splitting. METHODS Split donor storage times (splitting to grafting) and total storage times (death to grafting) were correlated with the 1-year functional and morphologic outcomes after DALK and DMEK surgery using a Spearman correlation coefficient and a Mann-Whitney U test. MAIN OUTCOME MEASURES Best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and complication rates within 12 months of follow-up. RESULTS The mean split donor storage time was 35 ± 47 hours (range, 0-162 hours) after splitting for anterior donor grafts and 21 ± 40 hours (range, 0-158 hours) for posterior grafts. The mean total storage time was 352 ± 108 hours (range, 108-678 hours) for anterior lamellas and 339 ± 109 hours (range, 96-630 hours) for posterior lamellas. One year after DALK, the mean BSCVA was 20/30 (range, 20/50-20/20), endothelial cell loss was 8% (range, 2%-16%), and the complication rate (Descemets folds, epitheliopathy, loose sutures) was 18%. One year after DMEK, the mean BSCVA was 20/25 (range, 20/40-20/16), endothelial cell loss was 41% (range, 17%-63%), and the complication rate (partial graft detachment) was 62%. For DALK and DMEK, no significant association was observed between split donor storage time as well as total storage time and BSCVA (P ≥ 0.409), endothelial cell loss (P≥0.236), or complication rate (P ≥ 0.647) within 1 year of follow-up. CONCLUSIONS Anterior and posterior donor tissue may be stored safely for up to 1 week in organ culture before use in DALK and DMEK surgery. This simplifies the clinical feasibility of split cornea transplantation to reduce donor shortage and cost in corneal transplantation in the future. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topical Ranibizumab inhibits inflammatory corneal hem- and lymphangiogenesis.

Purpose:  Ranibizumab (Lucentis®) is a Fab‐Fragment of a recombinant, humanized, monoclonal VEGF (anti‐vascular endothelial growth factor) antibody. This study analyzed the ability of topical Ranibizumab to inhibit lymphangiogenesis in addition to hemangiogenesis after acute corneal inflammation in vivo. In addition, the effect of Ranibizumab on the proliferation of human lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) in vitro was studied.

Spontaneous long-term course of persistent peripheral graft detachments after Descemet’s membrane endothelial keratoplasty

Background Peripheral corneal graft detachment after Descemets membrane endothelial keratoplasty (DMEK) is a frequently occurring postoperative complication. The natural course of these persistent peripheral detachments over time is not known. Methods 166 patients were surveyed by slit-lamp-adapted optical coherence tomography (SL-OCT) directly after surgery, during first postoperative week, 4 weeks, 3, 6 and 12 months, postoperatively. Patients with a persistent peripheral graft detachment 4 weeks after DMEK (n=16) were observed for their spontaneous course up to 1 year postoperatively. Results Persistent graft detachments could be characterised into two phenotypes: peripheral roll (n=11; 69%) and laminar detachment (n=5; 31%). Maximal length of the detachment did not change in peripheral rolls during observation period (12 months vs 4 weeks, 578±122 µm vs 593±106 µm, p=0.74), whereas laminar detachments spontaneously attached to the hosts stroma (12 months vs 4 weeks, 0 µm vs 1088±295 µm, p≤0.001). Central corneal thickness and (peripheral) corneal thickness above the detached area did not significantly change in either group. Conclusions Persistent peripheral graft detachments after DMEK occurred in 10% of patients and had two distinct OCT-phenotypes. Peripheral rolls did not change during the first 12 months, postoperatively. By contrast, peripheral laminar detachments attached spontaneously even months after surgery. Corneal thickness reduction was only observed above peripheral laminar detachment, but not above peripheral rolls.

Corneal nerve alterations in different stages of Fuchs’ endothelial corneal dystrophy: an in vivo confocal microscopy study

PurposeTo analyze potential alterations in corneal nerve morphology and function in different stages of Fuchs’ endothelial corneal dystrophy (FECD).MethodsThirty eyes with FECD underwent in vivo confocal microscopy using the Heidelberg Retina Tomograph II (HRT II; Heidelberg Engineering, Heidelberg, Germany) and the Rostock Cornea Module (RCM) to quantify the morphology of the central subbasal corneal nerve plexus (total nerve length, total nerve number, number of main nerve trunks, number of nerve branches) as well as esthesiometry (using the Cochet-Bonnet esthesiometer) of the central cornea to determine central corneal sensation as a measure of nerve function. Findings were correlated with an age-matched control group of 30 healthy individuals. Comparisons to biomicroscopical stage of FECD, visual acuity and central corneal thickness were performed using Spearman correlation.ResultsDepending on slit-lamp examination, all 30 eyes were classified into FECD stage 1–4 (stage 1: six eyes; stage 2: 15 eyes; stage 3: six eyes; stage 4: three eyes). Total nerve length (ρ = −0.8, p < 0.001), total nerve number (ρ = −0.7, p < 0.001), number of main nerve trunks (ρ = −0.6, p < 0.001), and number of nerve branches (ρ = −0.7, p < 0.001) decreased significantly with increasing FECD stages. Comparing to the visual acuity, significant positive correlations were found for total nerve length (ρ = 0.5, p = 0.012), total nerve number (ρ = 0.5, p = 0.005), number of main nerve trunks (ρ = 0.4, p = 0.017), and number of nerve branches (ρ = 0.5, p = 0.009). With central corneal thickness, there were significant inverse correlations for total nerve length (ρ = −0.6, p = 0.001), total nerve number (ρ = −0.5, p = 0.012), number of main nerve trunks (ρ = −0.4, p = 0.015), and number of nerve branches (ρ = −0.4, p = 0.017). Central corneal sensation was full in all FECD stage 1, stage 2 and stage 3 eyes, but mildly reduced in FECD stage 4 eyes.ConclusionsIncreasing severity of Fuchs’ endothelial corneal dystrophy (FECD) is concurrent with marked attenuation of the density, as well as mild diminishment of the function, of the subbasal corneal nerve plexus in late stage of the disease.

Corneal confocal microscopy detects small fiber damage in chronic inflammatory demyelinating polyneuropathy (CIDP)

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune‐mediated peripheral neuropathy with multifocal involvement. Reliable biomarkers for diagnosis, disease progression, and treatment response remain to be developed. We assessed the utility of corneal confocal microscopy (CCM) as a diagnostic marker for CIDP in 16 patients. CCM parameters including corneal nerve fiber density (NFD), nerve fiber length, number of main nerve trunks, number of nerve branches, nerve tortuosity, and dendritic cell density (DCD) were compared to those from 15 healthy controls and correlated with clinical and electrophysiological findings. CIDP patients had a significantly lower corneal NFD compared to healthy controls. The total nerve fiber length and the number of nerve branches were significantly decreased, whereas nerve tortuosity was increased in patients with CIDP. There was no positive correlation between corneal NFD and clinical or electrophysiological assessments. The average DCD was not significantly different in CIDP patients and controls. CCM measures suggest damage to small sensory afferents in the cornea in CIDP patients. Further studies are needed to compare different neuropathic conditions and to explore longitudinal changes of CCM parameters.

Corneal nerve alterations after Descemet membrane endothelial keratoplasty: an in vivo confocal microscopy study.

Purpose: Recent studies have identified diminishment of corneal nerves as another hallmark of Fuchs endothelial corneal dystrophy. This study aimed to analyze changes in corneal nerves after Descemet membrane endothelial keratoplasty (DMEK). Methods: Twenty-five patients were assessed for nerve alterations preoperatively and 1 week, 4 months, and 20 months after DMEK surgery. Morphology of the central subbasal nerve plexus was quantified by in vivo confocal microscopy. Results: The total nerve length (481.2 ± 81.9 vs. 1536.0 ± 123.8 &mgr;m per frame, P < 0.0001), total nerve number (2.2 ± 0.3 vs. 7.2 ± 0.5 per frame, P < 0.0001), number of main nerve trunks (1.8 ± 0.2 vs. 3.5 ± 0.3 per frame, P < 0.0001), and number of nerve branches (0.5 ± 0.2 vs. 3.7 ± 0.4 per frame, P < 0.0001) were significantly decreased 1 week after DMEK compared with preoperative measurements. Ten months postoperatively, corneal nerves recovered to preoperative values. Central corneal sensation significantly reduced postoperatively (5.1 ± 1.0 vs. 6.0 ± 0.0, P = 0.001), but recovered during follow-up (10 months: 6.0 ± 0.0). Conclusions: DMEK diminishes the density and the function of subbasal corneal nerves early after transplantation. However, a complete recovery of corneal nerve density and function up to preoperative values occurs within 4 to 10 months.

Regression of mature lymphatic vessels in the cornea by photodynamic therapy

Background Corneal (lymph) angiogenesis is a predominant risk-factor for immune rejection after transplantation. Techniques to regress pre-existing pathological corneal lymphatic vessels prior to transplantation are missing so far. Therefore we analysed the possibility to regress corneal lymphatic vessels by photodynamic therapy (PDT), after intrastromal verteporfin injection. Methods Combined hemangiogenesis and lymphangiogenesis was induced in female BALB/c mice using the murine model of suture-induced inflammatory neovascularisation. Thereafter, the treatment group received an intrastromal injection of verteporfin (controls: phosphate buffered saline (PBS)) followed by PDT. Corneas were excised at different time points (1 day, 5 days and 10 days) after PDT and corneal whole mounts were stained with CD31 and LYVE-1 to quantify hemangiogenesis and lymphangiogenesis. Results Whereas blood vessels showed no significant reduction after PDT, lymphatic vessels could significantly be reduced with PDT after intrastromal verteporfin injection: 1 day after PDT, lymphatic vessels were reduced by 62% (p=0.20). After 5 days and 10 days, lymphatic vessels were reduced by 51% and 48% (p<0.001), respectively. Conclusions This study for the first time shows that PDT after corneal intrastromal verteporfin injection can selectively regress lymphatic vessels. This may become a new ‘preconditioning strategy’ to reduce pre-existing corneal lymphatic vessels prior to transplantation and thereby reduce allograft rejection in high-risk patients.

Descemet membrane endothelial keratoplasty in eyes with glaucoma implants.

Purpose This study aims to analyze the feasibility of Descemet membrane endothelial keratoplasty (DMEK) in the management of corneal endothelial decompensation in eyes with glaucoma implants. Case Report A 62-year-old male with bullous keratopathy after trabeculectomy and Baerveldt shunt implantation for contusion glaucoma of the right eye (case 1) underwent surgical tube trimming with a DMEK procedure. A 54-year-old male with Descemet stripping automated endothelial keratoplasty (DSAEK) failure and dislocation in the presence of an Ahmed glaucoma valve and an artificial iris in the right eye (case 2) was treated by removal of the DSAEK graft and subsequent DMEK procedure. In both eyes, the DMEK graft could be successfully inserted, unfolded, positioned in front of the glaucoma tube, and attached to the host stroma by air injection into the anterior chamber. Postoperatively, both corneas cleared with complete graft attachment and stable glaucoma tube position. After 3 days, peripheral graft detachment occurred in case 1 and was managed successfully with one intracameral air reinjection. Case 2 revealed intraocular pressure (IOP) elevation up to 30 mm Hg in the immediate postoperative period, treated successfully by antiglaucoma medications. Within 1-year follow-up, visual acuity improved from hand movements to 20/63 and 20/32, respectively; endothelial cell density decreased by 36% and 42%, respectively; and the IOP ranged between 7 and 14 mm Hg in both cases without treatment. Conclusions Descemet membrane endothelial keratoplasty seems to be feasible in the management of corneal endothelial decompensation in eyes with glaucoma implants. Graft attachment, IOP, and endothelial cell density should be followed up closely.

Ophthalmological manifestations of Parry-Romberg syndrome

Parry-Romberg syndrome is a rare disease characterized by slowly progressive atrophy affecting facial subcutaneous tissues, including the underlying muscles and osteocartilaginous structures. Various periocular, ocular, and neuro-ophthalmological manifestations have been described in Parry-Romberg syndrome. The most common periocular disorders include enophthalmos, eyelid, and orbit alterations. The most frequent ocular disorders include corneal and retinal changes, and the most common neuro-ophthalmological disorders involve optic nerve, ocular motor and pupillary dysfunction. Besides the characteristic facial abnormalities, systemic manifestations may occur, including neurologic, dermatologic, cardiac, endocrine, infectious, orthodontic, and maxillofacial disorders. So far, mainly brief case reports describe these ophthalmological findings. Therefore, we summarize the ocular, periocular, and neuro-ophthalmological findings in detail, describe diagnostic modalities, and outline therapeutic options.

Blockade of the VEGF isoforms in inflammatory corneal hemangiogenesis and lymphangiogenesis

BackgroundThe VEGF-A family plays a crucial role in the induction of pathological corneal neovascularization. The role of the different VEGF-A isoforms during lymphangiogenesis is only little-known. Current anti-angiogenic therapies in the eye and other organs inhibit all VEGF-A isoforms, and have effects on both blood and lymphatic vessels. Here we investigate whether selective targeting of the isoform VEGF 165 is able to inhibit corneal lymphangiogenesis under inflammatory conditions.MethodsThe mouse model of suture-induced corneal neovascularization was used to assess the antihem- and antilymphangiogenic effect of topically applied pegaptanib. Corneal blood and lymph vascularized areas were analyzed morphometrically. Furthermore, we analyzed the proliferative effects of VEGF A 121, 165, and 189 on blood and lymphatic endothelial cells (BEC/LEC) via a cell-proliferation assay.ResultsPegaptanib significantly inhibited inflammatory corneal hemangiogenesis (p < 0.01), but not lymphangiogenesis in vivo (p > 0.05), both topically as well as systemically, in the inflamed cornea. In vitro, BECs were more susceptible to pegaptanib than LECs.ConclusionsTargeting VEGF-A 165 significantly inhibits hem- but not lymphangiogenesis, suggesting VEGF-A 165 to be critical for hem-, but dispensable for lymphangiogenesis, at least in the inflamed cornea.