Ophthalmic drug effects on the amyloidogenesis of a transforming growth factor ß-induced protein (TGFBIp) peptide fragment.

Drugs that can treat one disease may either be detrimental or beneficial toward another due to possible cross-interactions. Therefore, care in choosing a suitable drug for patients with multiple diseases is crucial in successful patient management. This study explores several currently available ophthalmic drugs used to treat common ocular diseases to understand how they can affect the amyloidogenesis of a transforming growth factor ß-induced protein (TGFBIp) peptide fragment found in abundance in the corneal protein aggregation deposits of lattice corneal dystrophy (LCD) patients. Results from this study provided supporting evidence that some drugs intended to treat other diseases can enhance or inhibit fibrillar aggregation of TGFBIp peptide, which may have potential implication of affecting the disease progression of LCD by either worsening or ameliorating it. Comparisons of the different properties of ophthalmic compounds explored in this study may also provide some guidance for future design of drugs geared toward the treatment of LCD.

Uncovering the role of ferroptosis in Bietti crystalline dystrophy and potential therapeutic strategies.

PURPOSE: Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. METHODS: Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. RESULTS: Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. CONCLUSION: This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.

Melatonin reduces endoplasmic reticulum stress and corneal dystrophy-associated TGFBIp through activation of endoplasmic reticulum-associated protein degradation.

Endoplasmic reticulum (ER) stress is emerging as a factor for the pathogenesis of granular corneal dystrophy type 2 (GCD2). This study was designed to investigate the molecular mechanisms underlying the protective effects of melatonin on ER stress in GCD2. Our results showed that GCD2 corneal fibroblasts were more susceptible to ER stress-induced death than were wild-type cells. Melatonin significantly inhibited GCD2 corneal cell death, caspase-3 activation, and poly (ADP-ribose) polymerase 1 cleavage caused by the ER stress inducer, tunicamycin. Under ER stress, melatonin significantly suppressed the induction of immunoglobulin heavy-chain-binding protein (BiP) and activation of inositol-requiring enzyme 1α (IRE1α), and their downstream target, alternative splicing of X-box binding protein 1(XBP1). Notably, the reduction in BiP and IRE1α by melatonin was suppressed by the ubiquitin-proteasome inhibitor, MG132, but not by the autophagy inhibitor, bafilomycin A1, indicating involvement of the ER-associated protein degradation (ERAD) system. Melatonin treatment reduced the levels of transforming growth factor-ß-induced protein (TGFBIp) significantly, and this reduction was suppressed by MG132. We also found reduced mRNA expression of the ERAD system components HRD1 and SEL1L, and a reduced level of SEL1L protein in GCD2 cells. Interestingly, melatonin treatments enhanced SEL1L levels and suppressed the inhibition of SEL1L N-glycosylation caused by tunicamycin. In conclusion, this study provides new insights into the mechanisms by which melatonin confers its protective actions during ER stress. The results also indicate that melatonin might have potential as a therapeutic agent for ER stress-related diseases including GCD2.

Epigallocatechin Gallate Remodels Fibrils of Lattice Corneal Dystrophy Protein, Facilitating Proteolytic Degradation and Preventing Formation of Membrane-Permeabilizing Species.

Lattice corneal dystrophy is associated with painful recurrent corneal erosions and amyloid corneal opacities induced by transforming growth factor ß-induced protein (TGFBIp) that impairs vision. The exact mechanism of amyloid fibril formation in corneal dystrophy is unknown but has been associated with destabilizing mutations in the fourth fasciclin 1 (Fas1-4) domain of TGFBIp. The green tea compound epigallocatechin gallate (EGCG) has been found to inhibit fibril formation of various amyloidogenic proteins in vitro. In this study, we investigated the effect of EGCG as a potential treatment in lattice corneal dystrophy (LCD) using Fas1-4 with the naturally occurring LCD-inducing A546T mutation. A fewfold molar excess of EGCG was found to inhibit fibril formation in vitro by directing Fas1-4 A546T into stable EGCG-bound protein oligomers. Incubation with 2 molar equiv of EGCG led to a 4-fold reduction in the aggregates' membrane disruptive potential, potentially indicative of significantly lower cytotoxicity with regard to corneal erosions. EGCG did not induce oligomer formation by wild-type Fas1-4, indicating that treatment with EGCG would not interfere with the native function of the wild-type protein. Addition of EGCG to 10-day-old fibrils reduced fibril content in a dose-dependent manner. Proteinase K was found to reduce the light scattering of nontreated fibrils by 31% but reduced that of fibrils treated with 8 molar equiv of EGCG by 85%. This suggests that EGCG remodeling of fibril structure can facilitate aggregate removal by endogenous proteases and thus alleviate the protein deposits' light scattering symptoms.

4-Phenylbutyric acid reduces mutant-TGFBIp levels and ER stress through activation of ERAD pathway in corneal fibroblasts of granular corneal dystrophy type 2.

Granular corneal dystrophy type 2 (GCD2) is caused by a point mutation (R124H) in the transforming growth factor ß-induced (TGFBI) gene. In GCD2 corneal fibroblasts, secretion of the accumulated mutant TGFBI-encoded protein (TGFBIp) is delayed via the endoplasmic reticulum (ER)/Golgi-dependent secretory pathway. However, ER stress as the pathogenic mechanism underlying GCD2 has not been fully characterized. The aim of this study was to confirm whether ER stress is linked to GCD2 pathogenesis and whether the chemical chaperone, 4-phenylbutyric acid (4-PBA), could be exploited as a therapy for GCD2. We found that the ER chaperone binding immunoglobulin protein (BiP) and the protein disulfide isomerase (PDI) were elevated in GCD2. Western bolt analysis also showed a significant increase in both the protein levels and the phosphorylation of the key ER stress kinases, inositol-requiring enzyme 1α (IRE1α) and double stranded RNA activated protein kinase (PKR)-like ER kinase, as well as in levels of their downstream targets, X box-binding protein 1 (XBP1) and activating transcription factor 4, respectively, in GCD2 corneal fibroblasts. GCD2 cells were found to be more susceptible to ER stress-induced cell death than were wild-type corneal fibroblasts. Treatment with 4-PBA considerably reduced the levels of BiP, IRE1α, and XBP1 in GCD2 cells; notably, 4-PBA treatment significantly reduced the levels of TGFBIp without change in TGFBI mRNA levels. In addition, TGFBIp levels were significantly reduced under ER stress and this reduction was considerably suppressed by the ubiquitin proteasome inhibitor MG132, indicating TGFBIp degradation via the ER-associated degradation pathway. Treatment with 4-PBA not only protected against the GCD2 cell death induced by ER stress but also significantly suppressed the MG132-mediated increase in TGFBIp levels under ER stress. Together, these results suggest that ER stress might comprise an important factor in GCD2 pathophysiology and that the effects of 4-PBA treatment might have important implications for the development of GCD2 therapeutics.

Choroidal neovascularization associated with extensive macular atrophy and pseudodrusen.

PURPOSE: To describe a case of extensive macular atrophy and pseudodrusen complicated by bilateral choroidal neovascularization (CNV). METHODS: A 53-year-old woman showed extensive macular atrophy at the posterior pole associated with disciform scar in the right eye and fibrotic juxtafoveal CNV in the left eye. RESULTS: The patient underwent a complete ophthalmological examination including fundus autofluorescence, fluorescein angiography, and spectral-domain optical coherence tomography, showing a disciform scar at the posterior pole of the right eye and an extensive macular atrophy associated with a fibrotic juxtafoveal CNV. The patient was previously treated with four and seven intravitreal bevacizumab injections, respectively, in the right eye and in the left eye. Molecular analyses of the ABCA4 gene revealed the variant c.1268A

Corneal collagen cross-linking for Terrien marginal degeneration.

PURPOSE: To report the long-term clinical outcome of a patient diagnosed as having Terrien marginal degeneration (TMD) who was subjected to corneal collagen cross-linking (CXL) with ultraviolet-A and riboflavin in both eyes. METHODS: Topographical changes were assessed by high-resolution Scheimpflug imaging and anterior segment optical coherence tomography. Eccentric epithelium-off CXL was performed in both eyes while protecting the corneal limbus. Irradiation was performed with a fluence of 5.4 J/cm(2), using 3 mW/cm(2) for 30 minutes. RESULTS: Five years of postoperative follow-up showed regression of the keratometric values, a local thickening of the corneal stroma, and bilateral improvement of corrected distance visual acuity. CONCLUSIONS: CXL may arrest progression in TMD and even reverse the catabolic process in the corneal stroma. CXL might represent an alternative therapeutic approach for the management of TMD.

Simultaneous conventional photorefractive keratectomy and corneal collagen cross-linking for pellucid marginal corneal degeneration.

PURPOSE: To present the results after simultaneous conventional photorefractive keratectomy combined with corneal collagen cross-linking for pellucid marginal corneal degeneration. METHODS: In this prospective, interventional case series, 6 patients (8 eyes) with pellucid marginal corneal degeneration were enrolled. All patients underwent simultaneous conventional photorefractive keratectomy combined with corneal collagen cross-linking; corneal epithelium was removed by transepithelial phototherapeutic keratectomy during treatment (Cretan protocol plus conventional photorefractive keratectomy). Visual and refractive outcomes were evaluated along with endothelial cell density preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. LogMAR mean uncorrected distance visual acuity improved significantly from 1.05 ± 0.33 preoperatively to 0.41 ± 0.27 (P = .018) at 12 months postoperatively. Mean corrected distance visual acuity did not change significantly (P > .05) postoperatively. Mean spherical equivalent improved significantly from -3.52 ± 2.29 diopters preoperatively to -1.57 ± 1.76 diopters (P = .028) at last follow-up. Mean corneal astigmatism was significantly reduced from -6.83 ± 2.33 diopters preoperatively to -4.71 ± 1.89 diopters (P = .018) at the last follow-up. No endothelial cell density alterations were observed throughout the follow-up period (P > .05). CONCLUSIONS: Simultaneous conventional photorefractive keratectomy combined with corneal collagen cross-linking seems to be an effective, safe, and promising treatment for the management of pellucid marginal corneal degeneration.

[The application of corneal collagen cross-linking in diseases other than keratoconus]. / Zastosowanie sieciowania wlókien kolagenowych rogówki w schorzeniach innych niz stozek rogówki.

Corneal collagen cross-linking is a method of treatment using ultraviolet radiation UVA and photosensitizing substance riboflavin to strengthen the chemical connections between the collagen fibers of corneal stroma. This treatment is focused on halting the progression of the diasases, called ectasias, characterized by irregular curvature and diminished thickness of the cornea. The most common indication for corneal collagen cross-linking is keratoconus. However, this technique may be also applied to pathologies other than keratoconus. The aim of this paper is to review the applicilcability of corneal collagen cross-linking in other conditions than keratoconus. Specifically, the conditions such as pellucid marginal degeneration, post refractive surgery ectasia as well as combined corneal collagen cross-linking and topography-based photorefractive keratectomy for topographies indicating forme fruste keratoconus are discussed. In addition, the effects of-corneal collagen cross-linking-as an adjunctive therapy in keratitis, corneal ulcers and corneal edema in bullous keratopathy are considered. The authors highlight the importance of treatment in clinical practice and the potential application of the treatment and modification of the protocols in the treatment of corneal diseases other than keratoconus.

Can Nerve Growth Factor (NGF) Be a Treatment Option for Pediatric Eye Diseases?

A critical review of mechanisms of action and pharmacokinetics of nerve growth factor (NGF), including topical administration, and the studies showing the NGF treatment for anterior and posterior segment diseases in adult and pediatric population are summarized in our paper. Nerve growth factor is commonly used for many different ocular conditions in the adult population to promote nerve regeneration or cellular rescue. Clinical trials for recombinant human NGF have also treated several challenging ocular conditions, such as neurotrophic keratopathy, glaucoma, and retinitis pigmentosa with cystoid macular edema. The safety and efficacy of NGF have been demonstrated in pediatric patients as well. This leads us to consider new applications of NGF for the treatment of pediatric eye diseases.

Recurrent Lisch Epithelial Corneal Dystrophy Treated With 5-Fluorouracil: A Case Report and Review of the Literature.

PURPOSE: The aim of the study was to describe a case of Lisch epithelial corneal dystrophy (LECD), review its clinical and histopathological features and diagnostic imaging, and introduce a novel treatment approach using topical 5-fluorouracil (5-FU). METHODS: A 65-year-old woman presented with a recurrent left-sided corneal lesion consistent with LECD. The lesion was evaluated clinically, with high-resolution optical coherence tomography (HR-OCT), and histologically. The lesion was successfully treated with two 1-week cycles of topical 5-FU. RESULTS: Slit-lamp examination showed an opalescent, whorl-shaped corneal lesion. HR-OCT revealed a trapezoidal area of normal thickness epithelial hyperreflectivity. Histopathology demonstrated a mucosal epithelium with foamy cytoplasm and increased cell size consistent with LECD. Treatment with topical 5-FU resulted in marked clearance of the corneal lesion on slit-lamp examination and HR-OCT. CONCLUSIONS: 5-FU may be considered as a treatment option for LECD.

Topical 1% cyclosporine eyedrops for the treatment of crystalline corneal dystrophy in dogs.

Background: Crystalline corneal dystrophy (CCD) is the most common type of corneal lipidic deposition in dogs. CCD is a primary metabolic disorder of the corneal fibroblast featuring an accumulation of extracellular and intracellular lipid deposits. Corneal lipid deposits create a corneal opacity and modify the interfibrillar collagen distance, inducing light scattering. Corneal vascularization is not usually associated with the disease, but, in case of chronicity, cell death may produce inflammation, and new corneal vessels are developed. To the best of the authors' knowledge, this is the first report of a medical approach for CCD treatment in veterinary medicine. Aim: To evaluate the efficacy of topical 1% cyclosporine eyedrops (1% CsA) for the treatment of CCD in dogs. Methods: Medical records of dogs with CCD were retrospectively reviewed (2009-2020). Corneal opacification description (COD) [size (mm), depth, and opacification degree (0-3)] was evaluated at 0, 3, 6, 9, 12, and 15 months postinitial diagnosis. Dogs were classified into three groups: the control group (G0), the group receiving topical 1% CsA once per day (G1), and the group receiving topical 1% CsA twice daily (G2). Results: Ninety-two client-owned dogs (163 eyes) of different breeds, ages, and gender fulfilled the inclusion criteria. When compared to G0, where the eyes significantly increased COD (p < 0.001), G1 and G2 significantly decreased COD (p < 0.001). In fact, the probability of reducing COD was about three times higher in G2 than in G1, being nearly the same for the right [odds ratio (OR) = 2.94; 95% confidence interval (95% CI) = 0.55-15.78] and left eye (OR = 2.92; 95% CI = 0.49-17.26). In addition, for each additional month of treatment in G2, the probability of reducing COD increased significantly (OR = 1.12; 95%CI = 1.00-1.26 for the right eye and OR = 1.16; 95%CI = 1.02-1.32 for the left eye). Conclusion: Long-term treatment with topical 1% CsA eyedrops significantly improved CCD in dogs, being the probability of reducing COD higher when applying the treatment twice daily.

Unilateral vortex keratopathy of unknown etiology.

A 54-year-old man with noncontributory medical history presented to an ophthalmologist in January 2022 after 10 days of irritation in his right eye. The patient recounts having felt something get into his eye and under his contact lens (CL) while he was climbing into his car, but he was unsure what the foreign body may have been. Initial examination by the clinician found uncorrected distance visual acuity of 20/100-2 with a corneal abrasion, 4+ corneal edema, and 3+ conjunctival injection, for which he was placed on topical antibiotics (ocuflox and tobradex) with a bandage CL. 1 week later, visual acuity was 20/80, corneal edema had improved, and he was noted to have corneal scarring and an epithelial defect. Tobradex was continued while prednisolone drops and preservative-free artificial tears were started. 1 week later, the patient had worsening visual acuity to 20/250 and was referred to our tertiary center. On initial consultation, the patient had an uncorrected distance visual acuity of 20/500 and an uncorrected near visual acuity of >J10 in the right eye. Slitlamp examination of the right eye was significant for vortex keratopathy and mild corneal pannus with 360-degree subtle conjunctivalization of the limbus ( Figure 1JOURNAL/jcrs/04.03/02158034-202210000-00022/figure1/v/2022-10-03T121249Z/r/image-tiff ). The corneal topograph was obtained showing significant surface irregularity on the Placido image ( Figure 2JOURNAL/jcrs/04.03/02158034-202210000-00022/figure2/v/2022-10-03T121249Z/r/image-tiff ). Examination of the left eye was unremarkable. The ocular history is significant for myopia of -4.0 diopters and CL use for 20 years. The patient admits to regularly wearing soft CLs for several days straight and only removing them for a few hours. Antibiotics were discontinued, corticosteroid drops were reduced in frequency, and the patient was continued on preservative-free artificial tears. What imaging might you consider? What is your differential diagnosis at this point? What would be the most appropriate surgical and/or medical interventions? What would you counsel in prognosis for this patient?

Topical Insulin-Utility and Results in Refractory Neurotrophic Keratopathy in Stages 2 and 3.

PURPOSE: The purpose of this study was to evaluate the clinical outcome of patients with refractory neurotrophic keratopathy (NK) in stages 2 and 3 treated with topical insulin. METHODS: Retrospective analysis of eyes with NK in stages 2 and 3 refractory to standard medical and/or surgical treatment which were treated with topical insulin (1 unit per mL). This treatment was applied 4 times per day and was continued until the persistent epithelial defect (PED) or ulcer resolved. The primary outcome of the study was the complete reepithelialization of the PED or persistent ulcer. "Best-corrected visual acuity" pretreatment and posttreatment, "days until complete reepithelialization" data, and anterior segment photographs were obtained. Outcome measures were compared before and after treatment in both groups using paired and independent samples t tests. RESULTS: Twenty-one eyes were included in this study, and 90% achieved complete reepithelialization of the PED and/or persistent ulcer within 7 to 45 days of follow-up. The mean number of days until complete reepithelialization was significantly lower in NK stage 2 (18 ± 9 days) when compared with NK stage 3 (29 ± 11 days) ( P = 0.025). The best-corrected visual acuity improved significantly in both NK stage 2 ( P < 0.001) and NK stage 3 ( P = 0.004). No side effects were reported during the follow-up. CONCLUSIONS: Our results suggest that topical insulin drops may be an effective therapeutic in refractory NK. This therapy may prove extremely useful because of its low cost and high accessibility.

Cutting Edge: Topical Recombinant Nerve Growth Factor for the Treatment of Neurotrophic Keratopathy-Biologicals as a Novel Therapy for Neurotrophic Keratopathy.

ABSTRACT: Ophthalmologists find management of neurotrophic keratopathy (NK) challenging because conventional therapy lacks efficacy and may result in permanent loss of vision. Recombinant nerve growth factor (cenegermin) targets the underlying pathogenesis of NK by regenerating corneal nerves and healing the corneal epithelium through promotion of proliferation, maturing corneal epithelial cells. It has been approved as Food Drug Association-approved treatment of NK. In this article, the background, clinical trials, and impact of recombinant nerve growth factor as the first neurotrophic factor for the restoration of corneal integrity, homeostasis, and corneal nerve regeneration are discussed.

Acute Calcific Band Keratopathy as an Adverse Effect of Recombinant Human Nerve Growth Factor (Cenegermin): A Multicenter Case Series.

PURPOSE: Cenegermin, (OXERVATE) a recently Food and Drug Administration-approved topical formulation of recombinant human nerve growth factor, has been used for the treatment of neurotrophic keratopathy (NK). Corneal deposits have been previously reported as a potential adverse effect; however, the clinical characteristics, visual significance, and treatment options have not been fully described. The purpose of this article is to better characterize corneal deposits occurring during treatment with cenegermin for neurotrophic keratopathy. METHODS: This was a retrospective, multicenter consecutive case series. RESULTS: We identified 5 patients from 3 institutions who developed a white opacity in varying layers of the cornea, consistent with calcium deposition, during treatment with cenegermin. In all cases, the opacity occurred rapidly over the course of a few weeks after initiation of treatment. Histopathologic examination of the cornea from one corneal patient demonstrated extensive calcification of the stroma extending to 90% depth. Before treatment, all patients had stage 2 or 3 NK (Mackie classification). The deposits were visually significant in all patients and did not resolve after cessation of cenegermin. There were no differences in age, sex, etiology of the NK, corneal transplant status, or concurrent medications between the patients who developed a deposit and 15 other patients with stage 2 or 3 NK who did not. One patient was successfully treated with superficial keratectomy with ethylenediaminetetraacetic acid chelation, one patient underwent penetrating keratoplasty, and one patient received a Boston keratoprosthesis. CONCLUSIONS: We report the rapid onset of a corneal opacity after initiation of treatment with cenegermin in patients with stage 2 or 3 NK, consistent with acute calcific band keratopathy. This visually significant adverse finding has not previously been described. We could not identify any risk factors for development. We recommend close monitoring of patients receiving cenegermin therapy because the opacity may be irreversible and may require keratoplasty for visual rehabilitation.

Melatonin protects against oxidative stress in granular corneal dystrophy type 2 corneal fibroblasts by mechanisms that involve membrane melatonin receptors.

Considering that oxidative stress plays a role in corneal fibroblast degeneration during granular corneal dystrophy type 2 (GCD2) and melatonin is an effective antioxidant, we examined the ability of melatonin to protect against oxidative stress-induced cell death of primary cultured normal and GCD2-homozygous corneal fibroblasts. Melatonin treatment protected primary cultured normal and GCD2 corneal fibroblasts from paraquat (PQ)-induced oxidative stress and caused increased expression levels of Cu/Zn-superoxide dismutase (SOD1) and glutathione reductase (GR) in both types of cells. Interestingly, catalase expression increased in normal corneal fibroblasts, but decreased in GCD2 corneal fibroblasts after melatonin treatment. Melatonin also reduced the levels of intracellular reactive oxygen species and H(2)O(2) in both cell types. In addition, the selective melatonin receptor antagonist luzindole blocked melatonin-induced expression of SOD1 and GR. The expression levels of melatonin receptors 1A (MT1) and 1B (MT2) were significantly higher in GCD2 corneal fibroblasts than in normal cells. These results suggest that increased expression of melatonin receptors may be involved in the defense mechanisms against oxidative stress in GCD2 corneal fibroblasts, and melatonin may have potential therapeutic implications for GCD2 treatment.

Superficial keratectomy, PTK, and mitomycin C as a combined treatment option for Salzmann's nodular degeneration: a follow-up of eight eyes.

PURPOSE: To analyze the treatment outcomes (safety and efficacy) of manual superficial keratectomy, phototherapeutic keratectomy (PTK), and intraoperative application of mitomycin C (MMC) for Salzmann nodular degeneration (SND). METHODS: In this retrospective study, we analyzed the records of eight eyes of five patients with Salzmann nodular degeneration (SND) who were treated between December 2006 and May 2008 at the University Eye Clinic Hamburg, Eppendorf, Germany. This case study includes data previously published within a single case report. Patients were followed-up pre- and postoperatively by slit-lamp biomicroscopy, digital photography, and corneal topography. All of the eight eyes were followed-up for at least 12 months, whereas in four eyes, follow-up was done for more than 24 months. PTK was performed with a 193-nm Ar-F excimer laser (Allegretto 200; WaveLight AG, Erlangen, Germany) within a 7-mm optical zone. Mitomycin C 0.02% was applied after PTK for 30 s. Postoperatively, a therapeutic contact lens was administered until corneal epithelial healing, which occurred usually at the forth postoperative day. Then local steroid therapy (prednisolone 1%) eye drops fours times per day was given for the following 4 weeks. RESULTS: Mean BCVA preoperatively was 0.61 logMAR (i.e., 20/80 Snellen equivalent or 0.25 decimal). There was a significant increase of BCVA by average of four reading lines (far distance) up to ten reading lines (p < 0.001). Mean BCVA postoperatively was 0.2 logMAR (i.e., 20/32 Snellen equivalent or 0.63 decimal). Treatment of SND led to a dramatic reduction of hyperopia (myopic shift) corresponding to a marked increase of best-corrected visual acuity (BCVA). Preoperatively documented hyperopic progression was stopped and refraction remained stable during the follow-up period in all eyes. Corneal topography showed regular astigmatism. During follow-up after treatment, the corneas appeared clear on slit-lamp examination. CONCLUSIONS: Our follow-up and the small treatment numbers are not sufficient to finally prove the superiority of the combined treatment modality (superficial keratectomy, PTK, and MMC) for SND, but the results of our study are promising. Longer follow-up and a larger cohort are warranted for proving MMC to be an effective, successful, and safe method in the armamentarium for treating and preventing Salzmann degeneration.

Simplified, Readily Available Method for the Treatment of Band Keratopathy With Ethylenediaminetetraacetic Acid.

PURPOSE: To compare 3 methods for creating ethylenediaminetetraacetic acid (EDTA) solution using readily available Vacutainer tubes for the treatment of band keratopathy. METHODS: All 3 protocols used commercially available Vacutainer blood collection tubes coated with K2EDTA. An osmometer was used to measure and compare the concentration of EDTA created using 3 different protocols. The time required for preparation of the solution was measured and compared to evaluate its efficiency for everyday clinical use. In addition, volume of EDTA solution obtained was measured for method 1. The most promising protocol for clinical use was then used for treatment of a series of patients. RESULTS: Average osmolarity was 532, 285, and 422 for methods 1, 2, and 3, respectively (ANOVA P < 0.01, all Tukey honestly significant difference P < 0.01). For the respective mixtures, average concentration was 65, 35, and 52 mg/mL, and average time to create solution was 189, 38, and 83 seconds (ANOVA P < 0.01, all Tukey honestly significant difference P < 0.01). The most promising, method 3, was found to be safe and effective in removing calcium from the corneal stroma in a series of 5 patients with 6 eyes treated. It also yielded 25% more solution for clinical use than method 1. CONCLUSIONS: Method 3 using a single 10-mL Vacutainer tube with 18 mg of K2-EDTA had the best balance of effective concentration of EDTA, time to preparation, and simplicity of methodology, when compared with previously published methods 1 and 2. It also yielded a greater final volume of solution.