Peripheral Cornea Research Articles

Eight months follow-up of corneal nerves and sensitivity after treatment with cenegermin for neurotrophic keratopathy

BackgroudCenegermin (Oxervate, Dompè Farmaceutici, Milan, IT), a recombinant human NGF, is a potentially healing new drug for neurotrophic keratopathy (NK), a rare but challenging disease affecting the cornea. To date, studies that evaluate its mid-term effect on corneal nerves and sensitivity are lacking.ObjectiveTo evaluate the recovery and morphology of subbasal corneal nerves in patients treated with Cenegermin for NK and assess their correlation with corneal sensitivity.MethodsThis prospective, observational case series study was carried out between May 2018 and August 2020 at the Ophthalmic Clinic of the University of Verona. Clinical evaluation, sensitivity, and in vivo confocal microscopy (IVCM) were performed in the central and all four corneal sectors at baseline, the end of therapy (8 weeks), and 2, 4, and 8 months after therapy. Consecutive patients with NK (stage 2–3), treated with Cenegermin (1 drop 6 times daily for 8 weeks), were enrolled. During each visit, Corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber fractal dimension (CNFraD) and Cochet-Bonnet esthesiometry (CBE) were measured.ResultsWe enrolled 18 patients. Complete NK healing was noted in 14/18(78%) patients after 8 weeks of treatment; then in 14(78%), 15(83%), and 13(72%) patients at 2-, 4-, and 8-months, respectively. Starting at 8 weeks through 4-month follow-up there was progressive improvement in CBE in all corneal sectors (p ≤ 0.01), which continued thereafter. There was significant corneal nerve regrowth especially in the peripheral cornea: centripetal progression starting at 8 weeks (CNFL and CNFrad) and significant branching starting at 2 months (CTBD), which continued through to the end of follow up. Sector-coupled IVCM and CBE findings correlated at all evaluations (all r ≥ 0.62 starting at 2 months, with highest values in the peripheral sectors).ConclusionsAfter Cenegermin we observed a subbasal corneal nerve regeneration, a recovery of sensitivity and a lasting epithelial healing, suggesting that the effect of its action persists several months after discontinuation in patients with NK.

A unique pre-endothelial layer at the posterior peripheral cornea: ultrastructural study

This study was conducted to investigate the ultrastructure of a unique structures at the anterior side of the endothelium of the posterior peripheral cornea and compare their inner fibers to those of the limbus and sclera. The unique structures at the anterior side of endothelium was referred as a pre-endothelial (PENL) structures in the present manuscript. Ten anonymous-donor human corneoscleral rims (leftover after corneal transplants) were processed for electron microscopy. Semi-thin sections were examined using an Olympus BX53 microscope, and ultrathin sections were studied using a JOEL 1400 transmission electron microscope. A unique PENL structures was identified at the posterior peripheral cornea at a radial distance of approximately 70–638 µm, from the endpoint of Descemet’s membrane. The PENL thinned out gradually and disappeared in the center. The contained an electron-dense sheath with periodic structures (narrow-spacing fibers), wide-spacing fibers, and numerous microfibrils. Typical elastic fibers were present in the sclera and limbus but were not observed in the PENL. This study revealed the existence of a new acellular PENL, containing unique fibrillar structures that were unseen in the corneal stroma. From the evidence describe in this paper we therefore suggest that PENL is a distinct morphological structure present at the corneal periphery.

Spontaneous Partial Regression of Bilateral Grade III Corneal Dermoids Associated With Fetal Valproate Spectrum Disorder

The purpose of this study was to describe a rare case of a child with bilateral central corneal dermoids (grade III) in association with fetal valproate spectrum disorder (FVSD) and to report the spontaneous regression of these tumors. Clinical records of a 14-month-old child whose mother took sodium valproate all along her pregnancy were retrospectively reviewed. The diagnosis of FVSD was made based on phenotypic features and associated congenital malformations. Facial features included trigonocephaly, flat nose bridge and small upturned nose, cleft palate and lip, and micrognathia. Systemic anomalies included bilateral radial defects and club hands, pes equinovarus, hypospadias, secundum atrial septal defect, patent ductus arteriosus, and aortic insufficiency. Cytogenetic studies were normal. Ocular findings included bilateral central corneal dermoids sparing the limbus and peripheral cornea, bilateral aphakia, absence of left anterior chamber, and bilateral mass-like vitreal opacities. A computed tomography scan suggested minimal left microphthalmia. Owing to the high-risk category for general anesthesia and prioritization of other severe systemic anomalies, no ocular surgical intervention was performed. Over 5 years of follow-up, spontaneous partial regression of the corneal tumors was observed. The development of bilateral grade III corneal dermoids in a child with FVSD may be more than fortuitous and enlarges the list of ocular anomalies associated with FVSD. Corneal dermoids may regress spontaneously.

Complications and fitting challenges associated with the Limbal Peripheral System in Scleral Lens

Purpose: The limbal zone of the scleral lens is intended to vault over an important area of the cornea that houses limbal stem cells necessary for corneal epithelial regeneration and limbal vasculature that supplies oxygen and nutrients to the avascular peripheral limbal cornea. An inappropriate fitting relationship in this peripheral curve system can negatively impact the limbal physiology. This paper aims to provide an overview of ocular sequalae associated with inappropriate limbal clearance and to discuss strategies for scleral lens practitioners to identify, manage, and overcome the fitting challenges in the limbal peripheral system of a scleral lens.

Peripheral ulcerative keratitis: A review of aetiology and management

Background: Peripheral ulcerative keratitis (PUK) is a severe inflammatory disease of the peripheral cornea that can be caused by local factors or systemic inflammatory disease.Aim: The purpose of this review is to give an overview of the pathophysiology, aetiology, clinical features, diagnosis, and management of PUK.Method: A PubMed search was conducted using the keywords, ‘peripheral ulcerative keratitis’ and ‘Mooren’s ulcer’.Results: The peripheral cornea has unique characteristics the predispose to the development of PUK. These include fine capillary arcades that allow for deposition of immune complexes and subsequent activation of an inflammatory cascade with corneal melt. Several conditions have been implicated in the aetiology of PUK. The most commonly cited causes are rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and various dermatoses. In patients with RA, PUK usually presents in established disease, whereas in GPA, PUK may be the presenting feature in up to 60% of cases. In RA it heralds the onset of a systemic vasculitis with significant associated morbidity and mortality. The management of PUK follows an individualised stepwise approach. All patients require supportive measures to encourage healing and halt the process of keratolysis. Systemic autoimmune conditions need a systemic corticosteroid as a fast-acting agent to halt the inflammatory process while cytotoxic therapy maintains long term disease control. Failure to achieve disease control with CTT, necessitates the use of a biologic agent.Conclusion: Peripheral ulcerative keratitis is a severe inflammatory disease of the peripheral cornea that needs a thorough diagnostic workup and stepwise management approach.

In situ metabolic profile and spatial distribution of ocular tissues: New insights into dry eye disease

PurposeDry eye disease (DED) is a chronic multifactorial disorder affecting millions of people, yet the pathogenesis mechanisms still remain unclear. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is a novel in situ visualization approach combined high-throughput mass spectrometry and molecular imaging. We aimed to explore the in situ ocular metabolic changes via MALDI-MSI to accelerate the recognition of DED pathogenesis. MethodsExperimental dry eye was established in Wistar rats by subcutaneous injection of scopolamine. The induction of DED was assessed by tear film breakup time, sodium fluorescein, histopathological staining and cell apoptosis. MALDI-MSI was applied to explore in situ ocular metabolomic in DED rats, and histopathological staining from same sections were used for side-by-side comparison with MALDI to annotate different tissue structures in the eye. ResultsConsidering the complexity of ocular tissue, we visualized the metabolites in specific ocular regions (central cornea, peripheral cornea, fornix conjunctiva, eyelid conjunctiva and aqueous humor), and identified metabolites related to DED, with information of relative abundance and spatial signatures. In addition, integrative pathway analysis illustrated that, several metabolic pathways such as glycerophospholipid, sphingolipid phenylalanine, and metabolism of glycine, serine and threonine were significantly altered in certain regions in the dry eye tissue. Moreover, we discussed how the metabolic pathways with spatiotemporal signatures might be involved in the DED process. ConclusionsOur data exploit the advantages of in situ analysis of MALDI-MSI to accurately analyze the region-specific metabolic behaviors in DED, and provide new clues to uncover DED pathogenesis.

Ultrastructure of collagen fibrils, proteoglycans and lamellae of the human cornea treated with Iontophoresis ‐ UVA cross‐linking and hypotonic riboflavin solution

AbstractPurposeTo investigate the effect of iontophoresis‐UVA cross‐linking with hypotonic riboflavin solution on the ultrastructural changes in the lamellae, collagen fibrils (CF) and proteoglycans (PGs) in the central and peripheral stroma of the human corneal buttons.MethodsIontophoresis method was used for the trans‐epithelial application of hypotonic riboflavin in ex vivo corneal culture for 5 minutes. The corneas were irradiated using three methods; Group 1 (G1): an UV‐A irradiance of 3 mW/cm2 for 30 minutes; Group 2 (G2): an UV‐A irradiance of 10 mW/cm2 for 9 minutes; Group 3 (G3): without UV‐A irradiation. Three untreated corneas were used as a control group (G0). After CXL procedure, the corneas were processed for electron microscopy. CF diameter and PGs in each sample were analyzed using iTEM program.ResultsThe keratocyte organelles and stromal architecture in the peripheral cornea were better preserved than in the central cornea. The mean CF diameter in the peripheral cornea of the ‘G1 and G2’ was significantly higher compared to those in the central cornea. In G3, the central corneal CF diameter was significantly larger than the peripheral corneal CF diameter. There were also differences in the PGs area size between the central and peripheral cornea in all groups.ConclusionsRiboflavin + UVA application at 3mW2 /cm for 30minutes and 10mW2/cm for 9 minutes is a suitable method of CXL; however, the 10mW2/cm for 9 minutes combination seems to present stronger phototoxic effect and better prognosis for corneal healing. CXL treatment was more effective at the periphery than center.AcknowledgmentsThis research project was funded by National Plan for Science and Technology Program (Grant Number 15MED4229‐02), King Saud University.

A unique pre‐endothelial layer at the posterior peripheral cornea: ultra‐structural study

AbstractPurposeTo investigate the ultrastructure of a unique pre‐endothelial layer (PENL) of the posterior peripheral cornea and compare their fibers to those of the limbus and sclera.MethodsTen anonymous‐donor human sclera–corneal rings (leftover after corneal transplants) were processed for electron microscopy. Semi‐thin sections were examined using an Olympus BX53 microscope, and ultrathin sections were studied using a JOEL 1400 transmission electron microscope.ResultsA unique pre‐endothelial layer (PENL) was identified at the posterior peripheral cornea a radial distance of 70 µm – 638 µm, from the Descemet’s membrane endpoint (DME). At 272 µm distance from the DME, the posterior pre‐limbal cornea contained 5 layers; basement membrane (BM), pre‐Descemet’s layer (PDL), Descemet’s layer (DM), and a pre‐endothelial layer (PENL) between the DM and endothelium (EN). As the DM runs towards the central stroma, the PENL thins out gradually and disappears at a distance of 638 µm from DME. The layer contained an electron‐dense sheath with periodic structures (narrow‐spacing fibers), wide‐spacing fibers, and numerous microfibrils. The typical elastic fibers were composed of an elastic core surrounded by microfibrils. These were present in sclera and limbus but were not observed in the PENL.ConclusionsThe present study revealed the existence of a new acellular PENL, and it can be considered as another layer of the pre‐limbal peripheral posterior cornea. Knowledge of the PENL layer may help with understanding the pathology of endothelial dystrophies and pre‐DM dystrophies. PENL fibers were similar in structure to the fibers of trabecular meshwork described previously.

Update on overview of pterygium and its surgical management.

Pterygium is a bulbar conjunctival fibrovascular growth that crosses the limbus and extends onto the peripheral cornea, and in some cases leads to significant visual complications. The prevalence of this disease has been reported to be from 1.2% to about 40% in different parts of the world. Although there are various risk factors for pterygium, which include ultraviolet (UV) radiation, viral infection, hereditary factors, immune factors, aseptic inflammation, and environmental irritation, the pathogenesis of pterygium is mainly related to exposure to UV light. In addition to cosmetic problems, pterygium can lead to eye irritation, disrupt the transparency of cornea on the pupil area, and cause disorders such as corneal astigmatism and damage to the visual axis leading to vision impairment. In the last few years, the treatment of pterygium has been developed and various new solutions have been used. Surgery is the main treatment for pterygium. Various techniques such as Bare Sclera, Rotational Conjunctival Flap, Limbal Conjunctival Autograft, Amniotic Membrane Graft, and Free Conjunctival Autograft are used for the removal of pterygium. It also seems that the worrisome problem of recurrence has been significantly reduced with newer treatment methods. On the contrary, the use of auxiliary treatments such as mitomycin C, b-radiation, 5-fluorouracil, topical use of interferons, and Avastin are also effective in reducing the recurrence rate.

Comparative evaluation of decellularized porcine cornea and small intestine submucosa for repairing of corneal defect in rabbit model

A study was conducted from December 2013 to March 2014 to compare the healing potential of decellularized porcine cornea (DPC) and small intestinal submucosa (DPSIS) for repairing of partial thickness corneal defect in rabbit model. Eighteen clinically healthy adult New Zealand White rabbits of either sex were divided into two groups. The porcine corneas and small intestinal submucosa were collected from abattoir and made acellular by treating with 1% sodium dodecyl sulphate. Under general anesthesia, a 5 mm diameter lamellar keratectomy wound was created over the peripheral cornea of rabbits under operating microscope in both the groups. The defect was repaired with DPC in Gr A and with DPSIS in Gr B. Corneal clarity was better in Gr A with less stromal scarring and incited less immune response than those of Gr B. Histopathological findings confirmed increased corneal neovascularization and fibroblast proliferation in Gr B than Gr A. On the basis of clinical, pathological and scanning electron microscopic examinations, DPC showed better corneal healing than DPSIS for repairing of corneal defect in rabbits.

“Egg in the eye appearance” of traumatic pre-existing posterior capsular defect presenting as near-total cataract

A 10-year-old girl was brought by her parents with complaints of a sudden drop in vision in the left eye (LE) with the appearance of a white reflex for a 1-month duration. There was a history of needle stick injury to the LE 5 years ago which was conservatively managed elsewhere. Previously, she had a vision of 6/9, N6 LE, with glasses as per her old records. The best corrected visual acuity (BCVA) was 6/6, N6 right eye (RE), hand motion (HM), and <N36 LE at the time of presentation. There was a small corneal scar at the 3 o'clock position in the peripheral cornea of the LE. Dilated examination of LE revealed near-total cataract, an intact anterior lens capsule, and a large elliptical area of pre-existing posterior capsular defect (PPCD) resembling an “egg in the eye appearance” [Figure 1]. Ultrasonography (USG) B scan of the LE showed the characteristic “fishtail sign” and confirmed the herniation of the lens matter through posterior capsular dehiscence into the anterior vitreous cavity [Figures 2 and 3] with an intact retina.Figure 1: Intra-operative picture of the LE taken after nicking the anterior capsule showing the fibrosed edges of the large elliptical posterior capsular dehiscenceFigure 2: Ultrasound B scan of the LE showing conical protrusion of the breached posterior lens capsuleFigure 3: Ultrasound B scan of the LE showing “fishtail sign” with herniation of the lens matter into the anterior vitreous cavity through the posterior capsular dehiscenceThe patient underwent a careful continuous curvilinear capsulorhexis (CCC), bimanual irrigation–aspiration of the lens matter, and anterior vitrectomy with reduced parameters of low bottle height, low irrigation, and aspiration, taking care to avoid hydro-dissection and shallowing of the anterior chamber. Intra-operatively, the large posterior capsular dehiscence [Figure 4] was carefully evaluated and cleared off any vitreous incarceration. A foldable three-piece intraocular lens (IOL) was implanted in the ciliary sulcus [Figure 5]. Post-operatively, the patient did well and regained 6/6, N6 vision in the LE, and remained the same until the last follow-up after 1 year [Figure 6].Figure 4: Intra-operative picture of the LE showing the large elliptical posterior capsular defect after lens aspirationFigure 5: Intra-operative picture after intraocular lens implantation into the LEFigure 6: Clear visual axis on follow-up after 1 yearDISCUSSION The history of past needle stick injury in our patient with sudden transformation into near mature cataract later points toward the presence of a PPCD which gradually caused microleakage and rapid maturation of the cataract. A dilated examination using a slit lamp and under an operating microscope helped to identify the thick, well-demarcated, elliptical borders of the PPCD, through the near-total cataract simulating an “egg in the eye” appearance. The thickened and fibrosed margins of the PPCD have been attributed to the migration of the hyperplastic epithelial cells to this region.[1] USG B scan confirmed the PPCD with lenticular matter hanging in the vitreous cavity (fishtail sign).[2] Other clinical signs which have been described in the literature include white demarcation lines and white crystalline particles floating in the vitreous, but they may not be evident in all white cataracts with PPCDs.[2] A relatively smaller CCC, closed-chamber bimanual irrigation–aspiration with reduced parameters (low bottle height, irrigation, and aspiration), avoiding hydro-dissection and shallowing of AC, controlled anterior vitrectomy, and switching between the cut and aspiration modes to remove the prolapsed lens matter and vitreous are essential to ensure a clear visual axis and safe IOL implantation.[2] CLINICAL SIGNIFICANCE All total cataracts are not the same, and surgery without a thorough history, careful examination, and proper planning could be catastrophic to the patient. Surgical management in pediatric cataracts with PPCD remains a challenge due to the increased risk of lens matter drop in the vitreous cavity. Identifying the PPCD, explaining the potential risks to the patient, and taking adequate precautions to avoid lens matter drop are vital steps to a successful outcome. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient and her parents have given their consent for images and other clinical information to be reported in the journal. The patient and her parents understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. Acknowledgements The patient and her parents are acknowledged.

Ocular and Facial Herpes Zoster and Meningitis in an Adult after Zoster Vaccination

Purpose: To report a case of ocular and facial herpes zoster and meningitis after herpes zoster vaccination.Case summary: A 60-year-old man was administered Zostavax® on his left arm; he developed a vesicular rash over his left eye and forehead 4 days afterwards. He started antiviral drugs for the rash, and visited the hospital for severe headache and spread of the rash to involve the tip of his nose, face, and palate by day 7. He was taking Synthyroid® (Bukwang Pharmaceuticals, Seoul, Korea) since his thyroidectomy for thyroid cancer 6 years ago. He had never been diagnosed with chickenpox, but had an episode of red facial rash in childhood. Slit-lamp examination revealed conjunctival chemosis, hyperemia, and a pseudodendrite in the peripheral cornea. The anterior chamber was quiet, and there were no significant findings on his brain magnetic resonance imaging. Varicella zoster virus was detected in the cerebrospinal fluid by polymerase chain reaction. The patient was treated with oral acyclovir drugs and topical ganciclovir, levofloxacin, and bromfenac. One week later, the pseudodendrite disappeared and conjunctival chemosis improved. There was no recurrence during 6 months follow-up.Conclusions: Reactivation of ocular or facial herpes zoster or meningitis after zoster vaccination may occur, rarely. Immediate antiviral treatment is required in these cases.

A Clinical Case of Fitting Scleral Lens for Correction of Pellucid Marginal Degeneration

Background. Pellucid Marginal Degeneration (PMD) is a rare bilateral degenerative corneal disease. It causes corneal ectasia with bilateral, clear, inferior (typically 4 o’clock to 8 o’clock), peripheral corneal thinning. It usually affects about 80% of corneal stroma, which leads to the corneal ectasia above the thinning area as well as provokes the irregular astigmatism and visual impairment that are difficult to correct. Purpose. To study the possibilities of correction and social rehabilitation in a patient with PMD wearing scleral lenses. Materials and methods. The study included a patient with PMD, signs of corneal dysfunction and narrow-angle subcompensated glaucoma in the right eye, and PMD of the cornea resulted in a corneal leukoma – terminal glaucoma in the left eye. In addition to standard ophthalmic methods, we performed corneal topography and optical coherence tomography (OCT). For intraocular pressure measurement, ICARE IOP tonometer was used in several areas of the intact peripheral cornea. Results. Prior to lens fitting, UCVA in the right eye amounted to 0.06. Scleral lens helped achieve a high visual acuity of 0.9–1.0. The lens was well-tolerated by the patient. Conclusion. Scleral lenses may be a good choice for patients with irregular cornea caused by corneal dystrophy. Not only they are easy to use and have a good visual effect, but they also help patients with social rehabilitation.

Orthokeratology reshapes eyes to be less prolate and more symmetric

PurposeThis prospective study assessed the influence of wearing and then discontinuing orthokeratology (OK) lenses on retinal shape and peripheral refraction in myopic children. MethodsFifty-eight myopic children (age 8–12 years) were equally divided into an OK group and a single vision spectacles (SVS) group. After 12 months of OK, it was discontinued for 1 month. Peripheral eye length (PEL), relative peripheral refraction (RPR), and corneal parameters were measured in the right eye on the nasal and temporal retinal sides at baseline, 6 months, and 12 months (13 months in OK group) visits. ResultsIn the SVS group, faster elongation of the temporal side PEL made the eyes more asymmetric and prolate, developing a temporal pointed shape. In the OK group, the nasal retinal side PEL grew faster, the nasal RPR developed less hyperopic defocus, and the eye shape became more symmetric and less prolate. The central cornea became thinner and flattened, while the peripheral cornea became steeper. Changes in corneal thickness, relative peripheral corneal power, and K-values were no significant differences for the OK and SVS groups at 12 months. ConclusionsThe cornea reverted to be no difference with myopic children with SVS after 1 month discontinuation of OK. The retinal shape of SVS eyes became more asymmetric and prolate with myopia progression. OK remodelled retinal shape to be less asymmetric and less prolate.

Femtosecond laser-assisted peripheral additive stromal keratoplasty for treatment of primary corneal ectasia: Preliminary outcomes.

Purpose:To report the preliminary results of a new surgical modality for the treatment of primary corneal ectasia, which consists of implanting allogeneic corneal tissue into the peripheral corneal stroma using a femtosecond laser system or femtosecond laser-assisted peripheral allogeneic stromal additive keratoplasty or FA-PASAK.Methods:This prospective, noncomparative case series includes patients with primary corneal ectasia including keratoconus and pellucid marginal degeneration. In the operating room, one or two ring or crescent-shaped allogeneic corneal segments were prepared using a handmade double-bladed punch, which were then implanted by a specially designed device, into stromal channels in the peripheral recipient cornea fashioned with a femtosecond-laser system.Results:A total of 15 eyes of 13 patients with mean age of 31.73 years were operated. There were significant improvements in uncorrected (0.68 to 0.3 logMAR) and corrected (0.44 to 0.16 logMAR) visual acuity, mean sphere, mean spherical equivalent refractive error, and mean keratometry (steep, flat, and average). Topographic and refractive astigmatism did not change significantly. Complications included a single case of bacterial keratitis secondary to epithelial defect, which was controlled with topical antibiotics eventually leading to an uncorrected vision of 20/25 one year after surgery.Conclusion:The use of allogeneic corneal ring or crescent shape segments may be a safe and cost-effective treatment for primary corneal ectasia, whereas a nomogram is necessary to be devised for general use of the technique.

Refractive changes of a new asymmetric intracorneal ring segment with variable thickness and base width: A 2D finite-element model.

PurposeTo evaluate the local geometric effects of a unilateral intrastromal ring segment with a combined variation of ring thickness and base width in a finite element simulation, and to compare it against the isolated effect of thickness or base width variation alone.MethodsA two-dimensional finite-element model of a transversely isotropic cornea was created assuming either axisymmetric stress or plane strain condition. The model geometry was composed of a three-layered corneal tissue (epithelium, anterior and posterior stroma) fixed at the limbus. The implantation of a triangular-shape asymmetric ring segment with varying ring thickness (150 to 300 μm) and base width (600 to 800 μm) was simulated. Also, changes induced by thickness or base width alone were studied and compared their combined effect in the asymmetric ring segment. Geometrical deformation of the simulated cornea and sagittal curvature were the main parameters of study.ResultsIncreasing ring thickness and base width along the arc of the asymmetric ring segment produced a more pronounced flattening in this part of the ring. The asymmetric design did find a good balance between maximizing corneal flattening at one end and minimizing it at the other end, compared to the isolated effect of ring thickness and width. Ring thickness was the most robust parameter in flattening both, the central and peripheral cornea.ConclusionThe finite-element model permitted a theoretical study of corneal deformation undergoing implantation of realistic and hypothetical ring geometries. Intracorneal asymmetric ring segments with varying thickness and base width can be a good alternative in corneas with asymmetric keratoconus phenotypes.

Review of Mechanisms, Pharmacological Management, Psychosocial Implications, and Holistic Treatment of Pain in Fabry Disease.

Fabry disease is a progressive X-linked lysosomal storage disease caused by a mutation in the GLA gene, encoding the lysosomal hydrolase α-galactosidase A. The consequent reduced enzyme activity results in the toxic accumulation of glycosphingolipids, particularly globortriaosylceramide (Gb3 or GL3), in blood vessels, renal epithelia, myocardium, peripheral nervous system, cornea and skin. Neuropathic pain is the most common manifestation of Fabry disease and can be extremely debilitating. This often develops during childhood and presents with episodes of burning and sharp pain in the hands and feet, especially during exercise and it is worse with increased heat or fever. It is thought to be due to ischaemic injury and metabolic failure, leading to the disruption of neuronal membranes and small fibre neuropathy, caused by a reduced density of myelinated Aδ and unmyelinated C-fibres and alterations in the function of ion channels, mediated by Gb3 and lyso Gb3. It is important to confirm small fibre neuropathy before any Fabry disease treatment modality is considered. There is a clinical need for novel techniques for assessing small fibre function to improve detection of small fibre neuropathy and expand the role of available therapies. The current Fabry disease guidelines are in favour of pharmacological management as the first-line treatment for pain associated with Fabry disease. Refractory cases would benefit from a rehabilitation approach with interdisciplinary input, including medical, physiotherapy and psychological disciplines and including a Pain Management Programme.

Term Newborn with Corneal Opacity.

Term Newborn with Corneal Opacity.

Case Report of Brown McLean Syndrome

Purpose: To report two rare cases of Brown McLean syndrome after cataract surgery in a patient with aphakia.Case summary: (Case 1) A 54-year-old woman with Marfan’s syndrome who had aphakia and peripheral corneal edema after left eye cataract surgery 4 years ago. The patient had an elevated lesion in the peripheral cornea without involving the central cornea, and had symptoms of pain, irritation and tearing. Specular microscopy showed normal endothelial cell density and morphology in the edematous cornea. The peripheral corneal edema improved after use of antibiotics, autoserum eyedrops and 5% NaCl eyedrops. (Case 2) A 61-year-old woman with aphakia in her left eye after bilateral cataract surgery 11 years ago, underwent surgery for a macular hole in both eyes. The patient developed peripheral corneal erosions and edema in the left eye 2 months after the surgery. Specular microscopy showed normal endothelial cell density and morphology. The peripheral corneal edema was static over the years while using 5% NaCl eyedrops and artificial tears, and did not progress to involve the central cornea.Conclusions: Brown McLean syndrome is a rare disease but the possibility should be considered if a patient with aphakia after cataract surgery has peripheral corneal edema for several years.

Preclinical Evaluation of the Safety and Efficacy of Cryopreserved Bone Marrow Mesenchymal Stromal Cells for Corneal Repair.

PurposeMesenchymal stromal cells (MSCs) have been shown to enhance tissue repair as a cell-based therapy. In preparation for a phase I clinical study, we evaluated the safety, dosing, and efficacy of bone marrow–derived MSCs after subconjunctival injection in preclinical animal models of mice, rats, and rabbits.MethodsHuman bone marrow–derived MSCs were expanded to passage 4 and cryopreserved. Viability of MSCs after thawing and injection through small-gauge needles was evaluated by vital dye staining. The in vivo safety of human and rabbit MSCs was studied by subconjunctivally injecting MSCs in rabbits with follow-up to 90 days. The potency of MSCs on accelerating wound healing was evaluated in vitro using a scratch assay and in vivo using 2-mm corneal epithelial debridement wounds in mice. Human MSCs were tracked after subconjunctival injection in rat and rabbit eyes.ResultsThe viability of MSCs after thawing and immediate injection through 27- and 30-gauge needles was 93.1% ± 2.1% and 94.9% ± 1.3%, respectively. Rabbit eyes demonstrated mild self-limiting conjunctival inflammation at the site of injection with human but not rabbit MSCs. In scratch assay, the mean wound healing area was 93.5% ± 12.1% in epithelial cells co-cultured with MSCs compared with 40.8% ± 23.1% in controls. At 24 hours after wounding, all MSC-injected murine eyes had 100% corneal wound closure compared with 79.9% ± 5.5% in controls. Human MSCs were detectable in the subconjunctival area and peripheral cornea at 14 days after injection.ConclusionsSubconjunctival administration of MSCs is safe and effective in promoting corneal epithelial wound healing in animal models.Translational RelevanceThese results provide preclinical data to support a phase I clinical study.