Ovol2 promoter mutations in mice and human illuminate species-specific phenotypic divergence.

Pathogenic variants in the highly conserved OVOL2 promoter region cause posterior polymorphous corneal dystrophy (PPCD) 1 by inducing an ectopic expression of the endothelial OVOL2 mRNA. Here we produced an allelic series of Ovol2 promoter mutations in the mouse model including the heterozygous c.-307T>C variant (RefSeq NM_021220.4) causing PPCD1 in humans. Despite the high evolutionary conservation of the Ovol2 promoter, only some alterations of its sequence had phenotypic consequences in mice. Four independent sequence variants in the distal part of the Ovol2 promoter had no significant effect on endothelial Ovol2 mRNA level or caused any ocular phenotype. In contrast, the mutation c.-307T>C resulted in increased Ovol2 expression in the corneal endothelium. However, only a small fraction of adult mice c.-307T>C heterozygotes developed ocular phenotypes such as irido-corneal adhesions, and corneal opacity. Interestingly, phenotypic penetrance was increased at embryonic stages. Notably, c.-307T>C mutation is located next to the Ovol1/Ovol2 transcription factor binding site. Mice carrying an allele with a deletion encompassing the Ovol2 binding site c.-307_-320del showed significant Ovol2 gene upregulation in the cornea endothelium and exhibited phenotypes similar to the c.-307T>C mutation. In conclusion, although the mutations c.-307T>C and -307_-320del lead to a comparably strong increase in endothelial Ovol2 expression as seen in PPCD1 patients, endothelial dystrophy was not observed in the mouse model, implicating species-specific differences in endothelial cell biology. Nonetheless, the emergence of dominant ocular phenotypes associated with Ovol2 promoter variants in mice implies a potential role of this gene in eye development and disease.

AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal degenerative disease characterized by yellow-white crystal deposits in the posterior pole, degeneration of the retinal pigment epithelium (RPE), and sclerosis of the choroid. Mutations in the cytochrome P450 4V2 gene (CYP4V2) cause BCD, which is associated with lipid metabolic disruption. The use of gene-replacement therapy in BCD has been hampered by the lack of disease models. To advance CYP4V2 gene-replacement therapy, we generated BCD patient-specific induced pluripotent stem cell (iPSC)-RPE cells and Cyp4v3 knockout (KO) mice as disease models and AAV2/8-CAG-CYP4V2 as treatment vectors. We demonstrated that after adeno-associated virus (AAV)-mediated CYP4V2 gene-replacement therapy BCD-iPSC-RPE cells presented restored cell survival and reduced lipid droplets accumulation; restoration of vision in Cyp4v3 KO mice was revealed by elevated electroretinogram amplitude and ameliorated RPE degeneration. These results suggest that AAV-mediated gene-replacement therapy in BCD patients is a promising strategy.

Multi-omics approach dissects cis-regulatory mechanisms underlying North Carolina macular dystrophy, a retinal enhanceropathy.

North Carolina macular dystrophy (NCMD) is a rare autosomal-dominant disease affecting macular development. The disease is caused by non-coding single-nucleotide variants (SNVs) in two hotspot regions near PRDM13 and by duplications in two distinct chromosomal loci, overlapping DNase I hypersensitive sites near either PRDM13 or IRX1. To unravel the mechanisms by which these variants cause disease, we first established a genome-wide multi-omics retinal database, RegRet. Integration of UMI-4C profiles we generated on adult human retina then allowed fine-mapping of the interactions of the PRDM13 and IRX1 promoters and the identification of eighteen candidate cis-regulatory elements (cCREs), the activity of which was investigated by luciferase and Xenopus enhancer assays. Next, luciferase assays showed that the non-coding SNVs located in the two hotspot regions of PRDM13 affect cCRE activity, including two NCMD-associated non-coding SNVs that we identified herein. Interestingly, the cCRE containing one of these SNVs was shown to interact with the PRDM13 promoter, demonstrated in vivo activity in Xenopus, and is active at the developmental stage when progenitor cells of the central retina exit mitosis, suggesting that this region is a PRDM13 enhancer. Finally, mining of single-cell transcriptional data of embryonic and adult retina revealed the highest expression of PRDM13 and IRX1 when amacrine cells start to synapse with retinal ganglion cells, supporting the hypothesis that altered PRDM13 or IRX1 expression impairs interactions between these cells during retinogenesis. Overall, this study provides insight into the cis-regulatory mechanisms of NCMD and supports that this condition is a retinal enhanceropathy.

Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of PRDM13 causing North Carolina macular dystrophy in Korea.

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families. Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools. Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13. Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.

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.

Establishment of mouse model of neurotrophic keratopathy through TRPV1 neuronal ablation.

Neurotrophic keratopathy (NK) is a challenging disease with the reduced innervation to the cornea. To establish a genetic and stable mouse model of NK, we utilized the TRPV1-DTR mice with intraperitoneal injection of diphtheria toxin (DT) to selectively eliminate TRPV1 neurons. After DT administration, the mice exhibited robust ablation of TRPV1 neurons in the trigeminal ganglion, accompanied with reduced corneal sensation and nerve density, as well as the decreased calcitonin-gene-related peptide (CGRP) and substance P levels. According to disease progression of TRPV1 neuronal ablation, tear secretion was reduced from day 3, which followed by corneal epithelial punctate lesions from day 7. From day 11 to day 16, the mice exhibited persistent corneal epithelial defects and stromal edema. By day 21, corneal ulceration and stromal melting were observed with the abundant inflammatory cell infiltration, corneal neovascularization, and enhanced cell apoptosis. Moreover, subconjunctival injection of CGRP delayed the NK progression with the characteristics of reduced severe corneal epithelial lesions and corneal inflammation. In addition, the impairments of conjunctival goblet cells, lacrimal gland, and meibomian gland were identified by the diminished expression of MUC5AC, AQP5, and PPARγ, respectively. Therefore, these results suggest that the TRPV1-DTR mice may serve as a reliable animal model for the research of NK pathogenesis.

Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy.

PURPOSE: To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). METHODS: A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. RESULTS: The patients' median age was 37 years (range, 20-76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to -0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031). CONCLUSIONS: BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy.

Sustained Release Formulation of Hydroxypropyl-ß-cyclodextrin Eye Drops Using Xanthan Gum.

Bietti's crystalline dystrophy (BCD) is an autosomal recessive chorioretinal degeneration caused by mutations in the CYP4V2 gene. It is characterized by cholesterol accumulation and crystal-like deposits in the retinas. Hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) exerts therapeutic effects against BCD by reducing lysosomal dysfunction and inhibiting cytotoxicity in induced pluripotent stem cell (iPSC)-RPE cells established from patient-derived iPS cells. However, the ocular retention of HP-ß-CyD is low and needs to be improved. Therefore, this study used a viscous agent to develop a sustained-release ophthalmic formulation containing HP-ß-CyD. Our results suggest that HP-ß-CyD-containing xanthan gum has a considerably higher sustained release capacity than other viscous agents, such as methylcellulose and sodium alginate. In addition, the HP-ß-CyD-containing xanthan gum exhibited pseudoplastic behavior. It was less cytotoxic to human retinal pigment epithelial cells compared with HP-ß-CyD alone. Furthermore, the slow release of HP-ß-CyD from xanthan gum caused a sustained decrease in free intracellular cholesterol. These results suggest that xanthan gum is a useful substrate for the sustained release formulation of HP-ß-CyD, and that HP-ß-CyD-containing xanthan gum has potential as an eye drop for BCD treatment.

Comparative evaluation of corneal and limbal epithelial thickness in brachycephalic dogs with and without corneal diseases using spectral domain optical coherence tomography.

OBJECTIVE: To evaluate alterations in epithelial thickness during corneal degeneration, corneal pigmentation, and additional features observed through spectral-domain optical coherence tomography (SD-OCT) in brachycephalic dogs. ANIMALS AND PROCEDURES: The study used 55 eyes from 49 brachycephalic dogs that underwent OCT-containing ophthalmic examinations. The examined eyes were classified into corneal degeneration, corneal pigmentation, and normal groups according to corneal lesions. For each eye, corneal epithelial thickness (CET) in the central cornea and maximum limbal epithelial thickness (maxLET) in 4 quadrants of limbus (superior, inferior, nasal, and temporal) were measured from OCT images. Additional abnormal findings on OCT images, including irregular epithelium, subepithelial hyperreflectivity, and conjunctivochalasis, were also recorded. RESULTS: The corneal degeneration group had significantly thinner nasal and temporal maxLETs than that of the normal group (p < .001). In the central corneal OCT image of the corneal degeneration group, an irregular epithelium was observed in 70.6% and subepithelial hyperreflectivity in 82.4%, both of which were significantly higher than the normal group (p < .001). In a comparative analysis, the nasal, temporal, and inferior maxLETs were significantly thinner in the corneal pigmentation group than those in the normal group (p < .001, p < .001, and p = .01, respectively). CONCLUSIONS: Morphological changes in the limbal epithelium were observed in dogs with corneal degeneration and corneal pigmentation. LET reduction could be associated with their pathogenesis and would be valuable as an additional parameter for corneal diseases.

Fuch's Endothelial Corneal Dystrophy in Cataract Patients Is Associated with Elevated Levels of Inflammatory Chemokines, but Not Growth Factors, in the Aqueous Humor.

The study investigated a profile of chemokines and growth factors in the aqueous humor (AH) of eyes with Fuch's endothelial corneal dystrophy (FECD) and cataracts in comparison with cataract patients as a control group. A total of 52 AH samples (26 FECD + cataract and 26 cataract/control) were collected before cataract surgery. None of the patients had any clinically apparent inflammation at the time of AH collection. The AH levels of MCP-1 (CCL2), MIP-1α (CCL3), MIP-1ß(CCL4), RANTES (CCL5), eotaxin (CCL11), IP-10 (CXCL10), FGF basic, G-CSF, GM-CSF, PDGF-bb, and VEGF were compared between the groups. The analyses were performed using the Bio-Plex 200 System from Bio-Rad. Among the studied parameters, the AH levels of RANTES, eotaxin, and IP-10 significantly increased in the FECD + cataract eyes, compared with the cataract controls (p < 0.05). Elevated levels of the RANTES, Eotaxin, and IP-10 indicate more intense inflammation in the eyes of patients in the FECD + cataract group. Moreover, these factors exhibit potential as predictive biomarkers for early detection of FECD in cataract patients. The discovery of elevated concentrations of biochemical markers in a patient, who has not yet received a clinical diagnosis, may suggest the need for heightened observation of the other eye to monitor the potential development of FECD.

An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes ZNF469 and PRDM5, from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases.

The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes ZNF469 and PRDM5 each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated ZNF469 and PRDM5 on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes' development of aneurysmal and dissection diseases.

[Intracorneal selective stromal transplantation]. / Vnutrirogovichnaya transplantatsiya stromy.

Deep anterior lamellar keratoplasty or penetrating keratoplasty are currently considered the optimal methods of surgical treatment of stromal dystrophies and corneal degeneration. Despite certain advantages and benefits of these methods, they also have significant limitations: involvement of superficial corneal layers in the surgery, need for suturing, development of post-keratoplasty astigmatism etc. PURPOSE: This study aimed to test and describe the new method of closed sutureless keratoplasty (intracorneal selective stromal transplantation), which was indicated in isolated dystrophic and degenerative pathology of the stroma. MATERIAL AND METHODS: Intracorneal selective stromal transplantation was performed in a 62-year-old patient with stromal degeneration and intact corneal layers between the altered stroma and the Descemet's membrane posteriorly, and the Bowman's layer anteriorly. The patient also had immature senile cataract. Corneal stroma was removed and replaced with a graft in the optical center of the lens, while the endothelium, the Descemet's membrane and the Bowman's layer remained intact. RESULTS: The proposed technique of intracorneal selective stromal transplantation makes it possible to replace only the pathologically altered stroma through closed surgical approach, without affecting the anterior and posterior surfaces of the cornea. Best-corrected visual acuity has increased in the patient from 0.01 to 0.6, while mean endothelial cell density has not changed in the course of 24-months follow-up. CONCLUSION: The proposed keratoplasty method can be used in patients with dystrophy or degeneration of the corneal stroma and preserved endothelial cells, intact Descemet's membrane and Bowman layer. Since the superficial corneal layers are not involved during the surgery, intracorneal selective stromal transplantation combined the advantages of both deep anterior lamellar keratoplasty and endothelial keratoplasty. The biologically favorable result in this first clinical case allows a preliminary conclusion on the technical possibility and functional effectiveness of the proposed method, but further long-term observation and more clinical cases are required.

Investigating phase separation properties of chromatin-associated proteins using gradient elution of 1,6-hexanediol.

BACKGROUND: Chromatin-associated phase separation proteins establish various biomolecular condensates via liquid-liquid phase separation (LLPS), which regulates vital biological processes spatially and temporally. However, the widely used methods to characterize phase separation proteins are still based on low-throughput experiments, which consume time and could not be used to explore protein LLPS properties in bulk. RESULTS: By combining gradient 1,6-hexanediol (1,6-HD) elution and quantitative proteomics, we developed chromatin enriching hexanediol separation coupled with liquid chromatography-mass spectrometry (CHS-MS) to explore the LLPS properties of different chromatin-associated proteins (CAPs). First, we found that CAPs were enriched more effectively in the 1,6-HD treatment group than in the isotonic solution treatment group. Further analysis showed that the 1,6-HD treatment group could effectively enrich CAPs prone to LLPS. Finally, we compared the representative proteins eluted by different gradients of 1,6-HD and found that the representative proteins of the 2% 1,6-HD treatment group had the highest percentage of IDRs and LCDs, whereas the 10% 1,6-HD treatment group had the opposite trend. CONCLUSION: This study provides a convenient high-throughput experimental method called CHS-MS. This method can efficiently enrich proteins prone to LLPS and can be extended to explore LLPS properties of CAPs in different biological systems.

Identification of a novel partial deletion of STS associated with pre-Descemet corneal dystrophy and X-linked ichthyosis.

Purpose: Pre-Descemet corneal dystrophy (PDCD) with X-linked ichthyosis (XLI) is associated with mutations in or deletions of the steroid sulfatase gene (STS). As only three cases of genetically confirmed PDCD associated with XLI have been reported, we sought to expand our understanding of the genetic basis of PDCD by screening STS in two previously unreported families. Materials and Methods: The affected individuals underwent cutaneous and slit-lamp examinations. Saliva samples collected from each affected individual served as a source of DNA for the amplification of the 10 coding exons of STS and flanking DNA markers. Results: The slit-lamp examination of three affected men (two of whom were brothers) from two families revealed bilateral punctate posterior corneal stromal opacities anterior to the Descemet membrane. Cutaneous examination demonstrated dry, coarse, scaly ichthyotic changes characteristic of XLI in all individuals. Genetic examination of the STS locus on the X chromosome in Case 1 revealed a deletion that spanned across DNA markers DXS1130-DXS237, which includes all the coding exons (exons 1-10) of STS. Genetic screening of Cases 2 and 3 revealed a partial deletion of the STS locus involving exons 1-7 and flanking DNA marker DXS1130 on the X chromosome. Conclusions: PDCD with XLI may be associated with either partial or complete deletion of STS. Despite the identification of point mutations, partial deletion, and complete deletion of STS in different affected families reported to date, there was no apparent difference in the affected phenotype between the families, suggesting that the identified variants likely all resulted in loss of function of steroid sulfatase.

12-year follow-up of the first endothelial keratoplasty without Descemet stripping in a 3-month newborn with Congenital Hereditary Endothelial Dystrophy (CHED).

BACKGROUND: Endothelial Keratoplasty (EK) is now considered as the standard treatment for Congenital Hereditary Endothelial Dystrophy (CHED) by many surgeons. We present the 12-year clinical outcome of the youngest operated patient with CHED in which we successfully performed a bilateral EK procedure without removing the recipient endothelium-Descemet complex. CASE PRESENTATION: In November 2010 we performed EK without Descemet Stripping in a 3-month female newborn, thinking that the lower manipulation obtained by leaving the recipient endothelium-Descemet complex could be the key factor for the success of our surgery. Such a particular technique was new in newborns. The surgery was a success, but the long-term visual result was not predictable at that time. We followed the patient at 4 months, and then yearly. At the latest visit in October 2022 the visual, cognitive, and motorial developments were normal, with Best-corrected Distance Visual Acuity of 0.4 LogMAR with - 0.75 D sf + 2.75 D cyl @ 105° in the right eye (RE) and 0.4 LogMAR with + 1.50 D sf + 2.50 D cyl @ 60° in the left eye (LE). The endothelial microscope showed an unexpected healthy endothelium, with a cell count of 2383 cells/mm2 in the RE and of 2547 cells/mm2 in the LE from a starting donor count of 2900 cells/mm2. No secondary procedures were performed during the 12-year follow-up. CONCLUSION: EK without Descemet stripping has proved to be a successful procedure over time in our newborn. The unexpected healthy endothelium suggests a role of the Descemet membrane in CHED.

Indications and outcomes of keratoplasty ≤ 5.5 mm diameter ("mini-keratoplasty").

PURPOSE: To report indications and clinical outcomes of corneal grafts ≤ 5.5 mm in diameter ("mini-KP") in a German tertiary referral center. METHODS: Patients who had undergone mini-KP to treat corneal ulcers with or without perforation between 2011 and 2018 at the Department of Ophthalmology, University of Düsseldorf, Germany, were identified from the local keratoplasty registry. All patient records were reviewed for age, gender, laterality, systemic and ophthalmological diseases, etiology of the corneal ulcerative disease, pre- and postoperative visual acuity over a follow-up time of up to 12 months, graft size, postoperative complications and the need for and timing of further corneal interventions. RESULTS: 37 eyes of 37 patients (male: n = 20; female: n = 17) with a mean age (± standard deviation) at presentation of 70 ± 18.8 years (range: 22-92 years) were identified. Most common etiologies were neurotrophic keratopathy (n = 15), dysfunctional tear syndrome (n = 9) and atopic keratoconjunctivitis (9). Mean graft diameter was 4.51 ± 0.63 mm (range: 3-5.5 mm). 23/37 eyes (62%) required no further intervention in the acute phase. 14/37 patients (38%) required secondary corneal intervention, due to complications. One-year graft survival was 78.4%. One eye had to be eviscerated due to recurrent corneal ulceration and endophthalmitis. 36 of 37 eyes were preserved. We found a highly significant correlation between type 2 diabetes and the development of postoperative complications (r = .46; p = .005). Corrected distance visual acuity (CDVA) improved from 1.42 ± 0.75 logMAR to 0.9 ± 0.65 logMAR postoperatively (t (23) = 5.76; p < .001). CONCLUSION: Mini-KP can be used successfully in eyes with advanced corneal ulcers due to various infectious and noninfectious etiologies to restore tectonic stability in the long-term and with moderate visual gains.

Safety and Efficacy of the Phototherapeutic Keratectomy for Treatment of Recurrent Corneal Erosions: A Systematic Review and Meta-Analysis.

BACKGROUND: Phototherapeutic keratectomy (PTK) has been increasingly used to treat severe recurrent corneal erosion syndrome (RCES) patients who do not respond to other treatments. However, the efficacy and complication of each study are currently uncertain due to varying rates. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of the PTK for recurrent corneal erosions. METHODS: This article performed a systematic literature research in Cochrane, Embase, PubMed, Scopus, and the Web of Science for the literature on PTK treatment of RCES until December 20, 2022. The extracted data including recurrence rate and the adverse event rate were used for meta-analysis. RESULTS: The recurrence rate was 18% (95% CI, 13%-24%) (129/700 eyes). Subgroup analysis showed that the RCE recurrence was 17% (95% CI, 9%-24%) after trauma and 22% (95% CI, 11%-32%) in the corneal dystrophy group. Treatment-related adverse events included subepithelial haze, hyperopic shift, and decrease of the best spectacle-corrected visual acuity. In this study, the incidence of these events was 13% (95% CI, 6%-21%), 20% (95% CI, 11%-28%), and 11% (95% CI, 5%-16%), respectively. CONCLUSIONS: PTK represented a valuable treatment option for patients with recurrent corneal erosions, especially those with traumatic injuries, which had minimal side effects.

Concomitant Bandage Contact Lens, Oral Nicergoline, and Topical Autologous Serum for Severe Neurotrophic Keratitis.

BACKGROUND: To report the outcomes of using the combination of oral nicergoline, autologous serum, and contact lens to enhance corneal epithelization in neurotrophic keratitis and to discuss the clinical potential of this management. METHODS: This was a prospective consecutive case series study of eight patients treated for neurotrophic keratitis at the "Conde de Valenciana" Institute of Ophthalmology. Oral nicergoline, autologous serum, and bandage contact lens were initiated at the same time, immediately after stage 3 diagnosis keratitis was confirmed clinically, and until corneal epithelialization was achieved or eminent corneal perforation was seen. In patients where diabetes was a cause, glycosylate hemoglobin was measured to asses metabolic control. Corneal esthesiometry and corrected distance visual acuity were assessed before and after treatment. RESULTS: This study included eight eyes of eight patients (5 men [62.5%], average age 57±17.9 years). All patients completed at least 1 month of follow-up after nicergoline and contact lens suspension. Of the eight eyes, no one had positive culture growth and complete epithelial healing was achieved in all cases. Half of patients had diabetes and had a poor metabolic control. Corneal sensitivity improved in all eyes almost 2 centimeters in Cochet-Bonnet esthesiometry ( P= 0.01). In addition, final visual acuity gains were obtained ( P= 0.100). CONCLUSIONS: The combination of oral nicergoline, autologous serum, and bandage contact lens simultaneously could be an alternative in the management of stage 3 neurotrophic keratitis when conventional medical treatment has no improvement of corneal epithelization.

Semiscleral Contact Lens Use After Direct Corneal Neurotization for Neurotrophic Keratopathy.

PURPOSE: To describe a case of a patient treated for neurotrophic keratopathy (NK) with direct corneal neurotization (CN), where a modification to the CN technique allowed for semiscleral contact lens use postoperatively. OBSERVATION: Our patient had successful CN with improved corneal sensation. During the procedure, a 1.0 mm gutter was created between the limbus and nerve graft to allow for semiscleral contact lens fitting. CONCLUSIONS: With the use of preoperative planning and a limbal gutter during CN, a semiscleral contact lens can serve as a well-tolerated postoperative management option to improve visual acuity and protect the corneal surface in patients with NK.

Disseminated idiopathic lipid keratopathy in a normolipemic cat.

OBJECTIVE: To report a case of idiopathic lipid keratopathy in a normolipemic cat. ANIMAL STUDIED: A 10-year-old neutered female European domestic cat. RESULTS: A cat was evaluated for bilateral white corneal deposits. Slit-lamp examination revealed multiple, well-defined, round, stromal, cream-colored deposits of different sizes associated with generalized superficial corneal vascularization. Blood lipids were normal, and no history of travel to tropical locations or ocular trauma was present. Topical betamethasone/gentamicin 0.1% suspension q 12 hours did not result in any improvement of clinical appearance after one week. Tomography following the initial therapy revealed dense, hyperreflective deposits with posterior shadowing in the anterior and mid stroma of both corneas. A four-week course of itraconazole 0.01% ophthalmic cream was prescribed q 12 hours with no improvement. Four months after the initial examination, a diagnostic superficial keratectomy and amniotic membrane implantation were performed. Histopathological analysis showed membrane bound vacuoles with infiltration of foamy macrophages suggesting a diagnosis of primary lipidosis. The post-surgical period was unremarkable, and ten days later, the patient was re-examined. Opacification from a corneal leukoma was observed in the excision site with mild fibrotic tissue. Two months post-keratectomy, no further changes were detected in the cornea, and the patient was managed only with topical lubricant. CONCLUSIONS: To our knowledge, this is the first report of idiopathic corneal lipidosis in a cat and may be considered as a differential diagnosis of corneal disease in felines.