Laboratory exploration of the use of ripasudil in descemetorhexis with a human ex vivo model.

The aim of the study was to investigate the effect of ripasudil on corneal endothelial cell survival and migration after two types of descemetorhexis on a human ex vivo model. Eleven human corneoscleral buttons were incubated in either 50 ml organ culture medium containing 10 µM ripasudil or 50 µl dimethyl sulfoxide (DMSO), the vehicle in ripasudil for 2 days prior to wound creation then for 14 days after. The wound was created with either full trephination scoring or by shallow trephination plus manual peeling. At day 14, immunohistochemistry with vimentin and Na+/K+/ATPase markers was conducted. Tissues were assessed at day 3, 7 and 14 for morphology, cell migration, cell viability and cell density. Full trephination scoring created more damage on tissues compared to shallow trephination with full Descemet membrane peeling. In the full trephination scoring group, no differences in cell viability were noted when ripasudil and DMSO were compared. With the peeling method, Ripasudil could protect the endothelial cell death and maintain the morphology compared to the control. At day 14, no differences in the peripheral cell viability and density were found between ripasudil and DMSO, although the ripasudil group presented significantly increased central cell count and cell viability. Increased cell migration was noted with ripasudil and the initial cell morphology of those migrated cells was similar to that of fibroblasts. In conclusion, ex vivo modelling suggested that peeling resulted in less cell damage than scoring and ripasudil maintained better morphology and promoted migration. These effects might be via transformation of endothelial cells into a more motile spindle-like phenotype.

Headache Attributed to Refractive Error: Improvement after Topography-Guided Photorefractive Keratectomy with Corneal Cross-Linking in Patients with Keratoconus.

PURPOSE: To investigate if topography-guided photorefractive keratectomy (TGPRK) alleviates headache, particularly headache attributed to refractive errors (HARE) in keratoconus. METHODS: Patients diagnosed with keratoconus undergoing TGPRK for refractive correction were included. Best spectacle corrected visual acuity (BSCVA) using the logMAR scale and refractive error were measured. Patients answered a questionnaire exploring headaches, characteristics, treatment, and the Headache Impact Test (HIT-6) before and 6 months after the surgery. RESULTS: 40 patients were included. Preoperatively, 24 patients (60%) met criteria for headaches: five for migraine, 14 for HARE, and five for tension-type headache (TTH). Patients with headaches preoperatively were more likely to require bilateral TGPRK, and the mean sphere and cylindrical power were higher. Postoperatively, 15 out of the 24 patients of the headache group experienced complete resolution of headaches, and only nine patients met diagnostic criteria for headaches: two for migraine, six for HARE, and one for TTH. The number of headaches reduced from 4.4 ± 2.4 to 0.5 ± 0.7 days/week (p < 0.001). Headache duration decreased from 108.5 ± 100.7 min to 34.4 ± 63.5 min (p = 0.002). Postoperatively, the consumption of analgesia decreased. The HIT-6 revealed an improvement in the quality-of-life post-procedure (p < 0.001). CONCLUSIONS: Surgical correction of irregular astigmatism in patients with keratoconus can alleviate or resolve headaches in a large proportion of patients, resulting in an improvement in their quality of life. Physicians should consider keratoconus in patients fitting criteria for HARE not alleviated by spectacle correction and suboptimal vision in glasses.

Challenges of DMEK Technique with Young Corneal Donors' Grafts: Surgical Keys for Success-A Pilot Study.

PURPOSE: To report on the surgical maneuvers recommended for a successful unfolding of very young donors in order to accomplish an uneventful Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. METHODS: Five patients (three females and two males, mean age 71.2 ± 6.7 years) with Fuchs endothelial cell dystrophy who underwent DMEK with very young donors (between 20 and 30 years old) were included. The following demographic data were assessed: donor's age, donor's endothelial cell density (ECD), preservation time, recipient's age and sex and unfolding surgical time. Best-corrected visual acuity (BCVA; decimal system), ECD and corneal central thickness (CCT) were assessed preoperatively and at 6-month follow-up. RESULTS: Donors' mean age was 23.6 ± 3.6 years (range 21 to 30) and the mean ECD was 2748.6 ± 162.6 cells/mm2. All of them underwent an uneventful DMEK as a single procedure performed by one experienced surgeon (MAG) with a mean unfolding time of 7.2 ± 4.9 min (range 4 to 15). The essential steps, including patient preparation as well as DMEK graft implantation, orientation, unrolling and centering are detailed. At 6 months, BCVA was 0.6 ± 0.2, ECD was 1945.0 ± 455.5 cells/mm2 and CCT was 497.0 ± 19.7 microns. CONCLUSIONS: We hereby present the keys to overcome tightly scrolled grafts of very young donors, which prove perfectly suitable for DMEK surgery. The graft shape tends towards a double-roll and specific maneuvers are strongly recommended.

Role of descemet's stripping without keratoplasty in management of endothelial disease.

PURPOSE OF REVIEW: To summarize recent literature on Descemet's stripping only (DSO) in management of endothelial disease with particular focus on Fuchs endothelial corneal dystrophy (FECD). RECENT FINDINGS: DSO is currently indicated in patients with early FECD, central guttae, and preserved peripheral corneal endothelial cell (CEC) count. Time to corneal clearance may be accelerated and maintained with addition of topical rho-kinase inhibitor (ROCKi). There are reports describing successful use of DSO to treat endothelial disease due to iatrogenic trauma. In patients with transcription factor 4 gene mutation, increased cytosine, thymine, guanine (CTG) triplet repeat load may be associated with DSO failure risk. Emerging pharmacotherapies and cell-suspension treatments may improve procedure effectiveness and expand clinical indications. SUMMARY: DSO can be used as the initial surgical treatment in management of symptomatic endothelial disease due to FECD where peripheral CEC function appears preserved. Stand-alone DSO or DSO combined with cataract surgery is effective and postoperative topical ROCKi supplementation will improve time to corneal clearance and CEC count.

Long-Term Results of Postoperative Rescuing of Inverted DMEK Grafts: Two Case Reports.

PURPOSE: The purpose of this study was to report the clinical outcomes of postoperative repositioning of 2 inverted Descemet membrane endothelial keratoplasty (DMEK) grafts in 2 patients with endothelial dysfunction. METHODS: Two patients underwent DMEK surgery in a tertiary referral corneal clinic. Initial surgery was performed by 2 different corneal surgeons, and a third surgeon repositioned both cases. In the early postoperative period, partial and subtotal detachments were observed at slitlamp and inverted graft orientation was confirmed by anterior segment optical coherence tomography. In both cases, uneventful reposition of the inverted graft was performed by an experienced DMEK surgeon on days 2 and 9 after initial DMEK surgery. RESULTS: Repositioning surgery was successful in both patients. The Moutsouris sign was used to confirm proper orientation. One patient had total graft adherence at day 1 postrepositioning. The second patient required a rebubbling procedure, despite the correct orientation confirmed by using anterior segment optical coherence tomography. Visual acuity and corneal thickness were stable in both cases (case 1: 20/30, 567 µm; case 2: 20/80, 543 µm). Both patients had clear corneas and functional cell counts 2 years after repositioning (451 cells/mm 2 and 1052 cells/mm 2 ). CONCLUSIONS: Postoperative repositioning of an inverted DMEK graft may be a viable procedure to delay or prevent regrafting.

Perioperative Cefazolin Prophylaxis in Pediatric Cardiac Surgery: A Prospective, Cohort Study.

BACKGROUND: This study's objective was to determine the effect of age, prolonged bypass, and hypothermia on serum cefazolin concentrations in children undergoing cardiac surgery. METHODS: A prospective, single-center, observational study was conducted, examining children undergoing cardiac surgery. Participants received cefazolin intravenously approximately 1 hour before skin incision, 3 hourly intraoperatively, and 8 hourly postoperatively. Blood samples were collected at 6 to 8 time points intraoperatively and at 6 time points in the first 24 hours postoperatively. Target unbound serum cefazolin concentrations were 2 mg/L. RESULTS: Sixty-eight patients were enrolled in the study, and 64 were included in the analysis. All maintained concentrations ≥ 2 mg/L throughout the operation. Nineteen patients (30%) did not maintain concentrations ≥ 2 mg/L in the first 24 hours after surgery. Older, larger children (P < .0001) were significantly less likely to achieve target unbound serum cefazolin concentrations. CONCLUSIONS: Intraoperative cefazolin concentrations reached the target concentration in all pediatric cardiac surgical cases. Postoperative cefazolin dosing appears to be insufficient to achieve minimum inhibitory concentrations in many patients.

New treatment algorithm for keratoconus and cataract: small-aperture IOL insertion with sequential topography-guided photorefractive keratectomy and simultaneous accelerated corneal crosslinking.

PURPOSE: To describe a new treatment algorithm aimed at optimizing refractive outcomes for patients with keratoconus and cataract. SETTING: Private practice in Sydney, Australia. DESIGN: Retrospective case series. METHODS: This procedural approach involves cataract extraction with small-aperture intraocular lens (IOL) insertion, IC-8 IOL (AcuFocus, Inc.), followed by topography-guided photorefractive keratectomy (T-PRK) with simultaneous corneal crosslinking (CXL). Cataract surgery was performed with an initial 2.4 mm clear corneal incision enlarged to 3.5 mm to accommodate IC-8 IOL insertion. Once eyes demonstrated stable corneal tomography and refraction, T-PRK was performed using Schwind excimer laser (500 Hz) with the Vancouver custom topographical neutralization technique, aiming to achieve low myopia. CXL was performed immediately after T-PRK using Optolink hypotonic riboflavin with LIGHTLink-CXL (Lightmed) with 5.4 J total energy delivered at an 18 mw/cm2 irradiance. RESULTS: Outcomes of 4 eyes are reported with all achieving rigid gas-permeable (RGP) contact lens independence, improved corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA), and regularization of corneal curvature with cone reduction. The mean CDVA improved from 0.43 preoperatively to 0.07 postoperatively (P = .00), and the mean UDVA improved from 0.81 preoperatively to 0.29 postoperatively (P = .04). Postoperative UNVA ranged from N.8 to N.12. CONCLUSIONS: This treatment algorithm demonstrates unique combination of existing corneal and cataract surgical procedures to achieve satisfactory refractive outcomes and RGP contact lens independence in patients with keratoconus and cataract.

Ex vivo excimer laser ablation of cornea guttata and ROCK inhibitor-aided endothelial recolonization of ablated central cornea.

PURPOSE: To determine whether excimer laser ablation of guttae is a viable strategy for removal of diseased tissue in Fuchs' endothelial corneal dystrophy (FECD) on excised human Descemet membranes and whether an excimer laser-created wound on healthy human corneas ex vivo is recolonized with corneal endothelial cells. METHODS: Descemet membranes of FECD patients and corneal endothelium of normal human corneas were ablated ex vivo using an excimer laser licensed for glaucoma surgery. Specimens were kept in cell culture medium supplemented with 10 µm of rho-kinase inhibitor ripasudil. Corneal endothelial cell regeneration was observed using light and electron scanning microscopy. Furthermore, the whole corneal samples were evaluated by haematoxylin/eosin staining and immunohistochemical analysis using antibodies against Na+ /K+ -ATPase. RESULTS: Guttae and corneal endothelium could be ablated with an excimer laser without total ultrastructural damage to the Descemet membrane or stroma. Nearly complete endothelial wound closure was accomplished after 26-38 days in treated corneas. Light and electron scanning microscopy suggested the establishment of a layer of flat endothelial cells. Additionally, Na+ /K+ -ATPase expression could only be observed on the inner side of the Descemet membrane. CONCLUSION: Our proof of concept study demonstrated that excimer lasers can be used to ablate diseased tissue from excised FECD Descemet membranes ex vivo. Additionally, corneal endothelial cells recolonize a previously ablated endothelial area in healthy human corneas ex vivo under treatment with ripasudil. Thus, our results are the first experimental basis to further investigate the feasibility of an excimer laser ablation as a graftless FECD treatment option.

5-Year Outcomes of Descemet Stripping Only in Fuchs Dystrophy.

PURPOSE: To report the 5-year outcomes of the first reported case of bilateral Descemet stripping only (DSO) for Fuchs endothelial corneal dystrophy (FECD) at our center. Visual, biomicroscopic, and confocal microscopic findings are described. METHODS: A retrospective case report. RESULTS: A 55-year-old woman with bilateral FECD was referred with decreased visual acuity and blurred vision that interrupted activities of daily living. She underwent sequential 4-mm DSO procedures 6 months apart, with early postoperative results previously reported. Subjective visual symptoms, visual acuity, and corneal edema were analyzed at 1 month, 3 months, 6 months, 12 months, 2 years, 3 years, and 5 years postoperatively. Best corrected visual acuity of 0.0 (logarithm of the minimum angle of resolution) and corneal clearance were achieved in the third month after the procedure. These results have remained stable in the 5-year follow-up period. CONCLUSIONS: Early postoperative results from DSO surgery are encouraging, but questions remain regarding its longevity. Publication of longer-term outcomes such as this is necessary to establish the validity of this procedure as an intervention for FECD.

Descemet's stripping without endothelial keratoplasty.

PURPOSE OF REVIEW: To summarize the recent literature regarding descemetorhexis stripping without endothelial keratoplasty (DWEK), increasingly referred to as Descemet's stripping only (DSO). To report the characteristic clinical, confocal and histologic findings associated with this procedure. RECENT FINDINGS: Reported clearance rates following DSO range from 63 to 100% in recent series, with variation between surgical techniques. Topical Rho-kinase inhibitor has been reported as successfully salvaging failing cases. Its use as an adjuvant to the surgery is gaining widespread adoption with the results of early series now arriving. Apart from a phenotype of central guttata with clear periphery, patient characteristics which determine success remain elusive. Surgical factors affecting success are increasingly well understood, with stromal injury felt to be a retardant to healing. Characteristic clinical signs have been observed and are described herein. Clinical, confocal and light microscopic images are obtained from patients in clinical trials of DSO with ripasudil. SUMMARY: DSO is gaining acceptance as a surgical option for a subset of patients with Fuchs' Dystrophy. The addition of Rho-associated kinase inhibitor appears to improve predictability but further results to this effect must be published and scrutinized.

Early postoperative results of Descemet's stripping endothelial keratoplasty in six dogs with corneal endothelial dystrophy.

OBJECTIVE: To describe and assess the clinical outcome and intraoperative and postoperative complications of Descemet's stripping endothelial keratoplasty (DSEK) in the treatment of canine corneal endothelial dystrophy. ANIMALS STUDIED: Six dogs (six eyes) diagnosed with progressive corneal edema resulting from abnormal dystrophic endothelial cells underwent Descemet's stripping endothelial keratoplasty. PROCEDURES: Six patients underwent Descemet's stripping endothelial keratoplasty (DSEK). The patients were examined preoperatively and postoperatively at 24 hours, 7 days, 1, 2, and 3 months after surgery. Corneal edema and ultrasonic pachymetry were evaluated preoperatively and postoperatively. The positions of DSEK grafts were evaluated 3 months after surgery using optical coherence tomography. Intraoperative and postoperative complications were noted. RESULTS: The degree of corneal edema and corneal thickness improved postoperatively in all the patients (n = 6). Fibrin was encountered intraoperatively in one out of the six eyes (1/6) and postoperatively in two out of the six eyes (2/6). One out of the six DSEK grafts was partially scrolled (1/6). Secondary ocular hypertension was observed in one out of the six eyes (1/6). Corneal vascularization was encountered in four out of six patients (4/6). CONCLUSIONS: Descemet's stripping endothelial keratoplasty is an effective surgical treatment option for corneal endothelial dystrophy in dogs. Corneal edema resolved and corneal thickness reduced significantly. The early postoperative results are encouraging. Further investigation is warranted to document any long-term complications and to study the longevity of the transplanted grafts.

Descemetorhexis Without Grafting for Fuchs Endothelial Dystrophy-Supplementation With Topical Ripasudil.

PURPOSE: To report the safety and efficacy of descemetorhexis without grafting as a primary intervention in Fuchs dystrophy, and the use of a ROCK inhibitor, ripasudil as a salvage agent in failing cases. METHODS: Twelve eyes of 11 patients underwent central descemetorhexis not exceeding 4 mm. All had Fuchs dystrophy-producing visual symptoms, requesting intervention. Exclusion criteria were a peripheral endothelial cell count <1000 and central edema. Corneal clearance and visual parameters were recorded monthly until corneal clearance was observed, then at intervals of 6 months. Cases failing to clear by month 2 were considered for salvage treatment. This consisted of treatment with 1 of 2 formulations of Rho-associated kinase inhibitor eye drops. Endothelial keratoplasty was planned as the final salvage procedure in unsuccessful cases. RESULTS: Nine of 12 eyes cleared spontaneously between 2 and 6 months. One eye failed to clear by month 5 and topical Y-27632 was administered, without success. Endothelial keratoplasty was performed. In 2 eyes, healing stalled at 3 and 2 months. In both cases, topical ripasudil administered 6 times a day for 2 weeks resulted in complete corneal clearance. In cases achieving corneal clearance, best spectacle corrected visual acuity improved from a mean of 0.26 to 0.125 (logMAR) with subjective improvement in quality of vision. CONCLUSIONS: In Fuchs dystrophy with visual degradation due to central guttae, descemetorhexis without grafting is a viable procedure for visual rehabilitation. Careful patient selection is required, but the advent of topical ripasudil as a salvage agent suggests that a broader application of the surgery may be possible. Further study into the use of this agent is now needed.

Descemetorhexis for Fuchs' dystrophy.

OBJECTIVE: To describe 2 cases of spontaneous corneal clearing after Descemetorhexis: 1 after iatrogenic trauma (Case 1) and 1 as an intentional surgical intervention for Fuchs endothelial dystrophy (Case 2). METHODS: Retrospective case reports. RESULTS: Full corneal clarity was observed to restore at approximately 1 month after surgery in both cases. Central endothelial cell counts were recorded as 753 and 731 cells/mm(2) in cases 1 and 2, respectively, at last follow-up. Best spectacle corrected visual acuity (BSCVA) at was 6/6 in both cases at 6 weeks and is retained at 9 months. CONCLUSIONS: Selective Descemetorhexis may offer visual rehabilitation without the need for a graft in select cases of Fuchs endothelial dystrophy. Descemetopexy in anticipation of corneal clearing is a viable initial strategy in cases of iatrogenic Descemet trauma with detachment.

Modification of the Miyake-Apple technique for simultaneous anterior and posterior video imaging of wet laboratory-based corneal surgery.

PURPOSE: The aim of this study was to describe a modification of the Miyake-Apple posterior video analysis for the simultaneous visualization of the anterior and posterior corneal surfaces during wet laboratory-based deep anterior lamellar keratoplasty (DALK). METHODS: A human donor corneoscleral button was affixed to a microscope slide and placed onto a custom-made mounting box. A big bubble DALK was performed on the cornea in the wet laboratory. An 11-diopter intraocular lens was positioned over the aperture of the back camera of an iPhone. This served to video record the posterior view of the corneoscleral button during the big bubble formation. An overhead operating microscope with an attached video camcorder recorded the anterior view during the surgery. RESULTS: The anterior and posterior views of the wet laboratory-based DALK surgery were simultaneously captured and edited using video editing software. The formation of the big bubble can be studied. CONCLUSIONS: This video recording camera system has the potential to act as a valuable research and teaching tool in corneal lamellar surgery, especially in the behavior of the big bubble formation in DALK.

Enzyme-assisted deep anterior lamellar keratoplasty-a new method of lamellar dissection-a wetlab-based pilot study.

PURPOSE: To explore the safety of a new technique of lamellar dissection, using enzymatic digestion of the corneal stroma and extracellular matrix. METHODS: This was a wetlab-based pilot study of hyaluronidase and trypsin-assisted deep anterior lamellar keratoplasty (DALK) in cadaveric human corneal tissue. Enzyme-assisted DALK was performed on 17 tissues. These underwent histologic analysis using a pneumatic dissection specimen as control. Rates of perforation and Descemet membrane (DM) exposure were recorded by clinical observation and by optical coherence tomography in selected cases. Where possible, pre- and postsurgical endothelial cell counts were obtained via specular microscopy. Two tissues from the same donor were halved, with each half soaked in a different solution (Optisol, balanced salt solution, hyaluronidase, and trypsin) for 13.5 hours to observe maximal effect. RESULTS: Successful exposure of DM was achieved in 8 specimens. In the remaining 9, manual dissection was possible to a residual depth of 25 to 90 µm where measured with optical coherence tomography. Three tissues had perforation of DM, all via manual maneuvers. No deleterious effects on residual host tissue were observed by light microscopy with no significant rates of endothelial cell loss in 8 tissues in which a predissection cell count was obtainable. The 2 enzymes had differing effects on soaked specimens that were reflected intraoperatively. CONCLUSION: Preliminary results of this ex vivo study are encouraging that enzymolysis may represent an effective innovation in DALK surgery with an acceptable safety profile. Further studies are required to refine the technique and application of the enzymes in vivo.

Clinical results of topography-based customized ablations in highly aberrated eyes and keratoconus/ectasia with cross-linking.

PURPOSE: To report results of a series of highly aberrated corneas treated with a topography-guided excimer laser ablation. METHODS: Retrospective, nonrandomized, consecutive series of eyes treated with topography-guided photorefractive keratectomy (TG-PRK) with the customized topographical neutralization technique (TNT). Cases included postoperative refractive surgery decentered ablations, optical zone enlargement, asymmetrical astigmatism, postoperative radial keratotomy (RK), postoperative keratoplasty, keratoconus combined with collagen cross-linking (CXL), and postoperative LASIK ectasia combined with CXL. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction were analyzed preoperatively and 6 months postoperatively. RESULTS: In decentered ablation cases, 94% of 37 eyes were within 1.00 diopter (D) of the attempted refractive outcome, with 76% within 0.50 D. Mean topographic, central, optical zone of uniform (monodioptric) power increased from 3.5 to 5.2 mm in 25 eyes. Thirty-one eyes treated for asymmetrical astigmatism showed improvement in cylinder from mean 1.31 to 0.52 D. Ten of 11 eyes treated for previous RK astigmatism achieved postoperative UDVA 20/40 or better. Twenty-seven eyes with postoperative keratoplasty astigmatism were treated, with 7 (25.9%) eyes gaining > or = 2 lines and 12 (44.4%) eyes gaining > or = 1 line of CDVA. Of eyes with keratoconus that were treated using TG-PRK with CXL, 42 (58%) eyes had UDVA 20/40 or better, and 66 (92%) eyes had CDVA 20/40 or better. Twelve (71%) of 17 eyes treated for postoperative LASIK ectasia using TG-PRK with CXL had UDVA 20/40 or better. Nine (53%) eyes gained > or = 2 lines of CDVA. CONCLUSIONS: Topography-guided laser treatment with custom TNT, combined with CXL in keratoconus and ectasia, is an effective, safe, and increasingly predictable option for highly aberrated corneas.

Ophthalmic presentation of Wegener's granulomatosis on a background of polymyalgia rheumatica.

We present a case of Wegener's granulomatosis (WG) in a 79-year-old man with limbitis and granulomatous conjunctivitis, on a background of polymyalgia rheumatica (PMR). The undifferentiated nature of ocular presentations of WG can be diagnostically challenging, especially in cases, such as this, where findings are initially inconclusive and evolve with time. This case highlights the significance of a history of PMR in patients with ocular inflammation. The systemic inflammatory systems of WG, including arthralgias, may mimic other conditions such as PMR. Patients with undifferentiated ocular inflammatory syndromes should be questioned regarding arthralgias, myalgias and stiffness. Such symptoms, or a background of PMR, should raise suspicion of WG.

Orbital cellulitis as a postoperative complication of sub-Tenon anaesthesia in cataract surgery.

Orbital cellulitis is a rarely reported sight-threatening complication of sub-Tenon anaesthesia. We report a case of orbital cellulitis in a patient who had received sub-Tenon anaesthesia for routine cataract surgery. We discuss the potential under-reporting of complications of sub-Tenon anaesthesia that had a delayed presentation, and the possible association between the use of hyaluronidase in the anaesthetic mixture and orbital cellulitis following sub-Tenon anaesthesia.

'Ancient' schwannoma of the orbit.

A 65-year-old woman presented with a 3 month history of right eye discomfort and protrusion. Examination revealed right proptosis with hypoglobus and diplopia in extremes of upgaze. Computed tomographic scanning revealed a large extraconal mass in the superotemporal orbit. The mass was excised through an extended superior skin crease incision. Histopathology revealed a benign tumour of Schwann cell origin showing advanced cystic degeneration, the so-called 'ancient schwannoma'. The authors could find only two previously reported cases of such tumours arising in the orbit.