Corneal Vascularization Research Articles

Treatment of Limbal Melanocytoma with Full Excision and a Fresh Homologous Corneoscleral Graft in a Dog

Background: Limbal melanoma has been diagnosed in dogs and due to progression may cause vision loss and eyeball removal. Definitive diagnosis is made through histopathological examination. Therapeutic options include full thickness resection and repair by homologous corneal tissue, synthetic graft material, and enucleation. In this report, we describe a case of limbal melanocitoma in a dog that has been treated successfully with fresh homologous corneoscleral graft.Case: A 5-year-old female Labrador was referred to the Ophthalmology Veterinary Section of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil, with a history of a pigmented mass located on the left eye. Ophthalmic examination revealed a pigmented mass located at the left temporal limbus with corneal involvement. Surgical excision followed by reconstruction using fresh homologous corneoscleral was recommended. The patient was premedicated with acepromazine (0.05 mg/kg, IM) and meperidine (20 mg/kg, IM). Anaesthesia was induced with propofol (10 mg/kg, IV) and maintained with isoflurane. Atracurium (0.2 mg/kg, IV) was administered to maintain a central eye position. The mass and a free margin were removed by full-thickness corneoscleral resection. A corneoscleral graft was harvested from a dogthat had been euthanised for reasons unrelated to this study and sutured with 9-0 polyglactin 910 using a simple interrupted pattern. The mass was immediately fixed in 10% neutral buffered formalin and submitted for histological sectioning and routine staining. Based on the histopathological analysis it was confirmed limbal melanocytoma. Postoperative treatment consisted of topical administration of 0.3% flurbiprofen every 6 h for 15 days, and a combination of topical ciprofloxacin/dexamethasone eye drops every 6 h for 30 days. Systemic carprofen (4 mg/kg per day, VO) was prescribed for 10 days. Topical tropicamide was used twice daily for 1 week. Cyclosporin 0.2% eye drops were applied twice daily for 2 months. Examination of the left eye two months after surgery revealed decreased corneal vascularization, and the results of pupillary light response and vision testing were normal. The values of intraocular pressure remained normal in all postoperativeevaluations. The patient was followed for 36 months postoperatively, during which time there was no recurrence.Discussion: Limbal melanomas are the most common ocular melanomas in dogs. Most of them develop slowly and are located closely to the superior limbus. The tumors tend to grow more rapidly in younger dogs and more slowly in older dogs. Labrador Retrievers and German shepherds appear to be affected more frequently than other breeds. The present case involved a 5-year-old Labrador breed. The clinical presentation included a pigmented limbal mass extending intothe adjacent cornea, sclera and conjunctival tissue. A tissue biopsy is necessary to confirm the diagnosis. In the present case, the diagnosis of limbal melanocytoma was based on clinical signs and confirmed by histopathological examination. The choice of treatment is influenced by the tumour size and location, availability of equipment and materials, clinician expertise and the cost of treatment. Some techniques for removing the mass and repairing the resultant corneoscleral defect has been described. In the present case, due to the location and size of the mass and the absence of intraocular invasion, surgical removal including a margin of normal tissue was performed. With this surgical procedure, the intention was to preserve the eyeball and maintain vision. In this case, surgical excision of a limbal melanocytoma combined with homologous corneoscleral graft was effective for repairing a full-thickness corneoscleral defect and preserving ocular function.

Idiopathic spontaneous filtering bleb: Is there an autoimmune etiology?

A 45-year-old male presented with complaints of defective vision for near. There was no prior history of trauma, recurrent redness, or surgery. He is a known patient of hypothyroidism and vitiligo. His best-corrected visual acuity was 6/6, N6 in both the eyes (BE). Slit-lamp examination revealed a diffuse, elevated, avascular thin bleb near the limbus in the superonasal quadrant with underlying scleral thinning in BE. Right eye (RE) showed clear cornea, quiet and deep anterior chamber, normal iris pattern, and clear lens. Left eye (LE) showed peripheral corneal vascularisation with lipid deposits at 10'o clock anterior to the area of scleral thinning and bleb formation, the rest of the anterior segment was normal [Fig. 1a and b]. Schirmer's test was normal and Seidel's test did not reveal any leak in BE. His intraocular pressure was 9 and 10 mm Hg in the RE and LE, respectively. Gonioscopy revealed open angles in BE with an area of hyperpigmentation around fistula at 2 o'clock in the RE and increased pigmentation with prominent iris processes in the nasal quadrant in LE [Fig. 1c and d]. The fundus examination revealed an average size disc with a cup to disc ratio of 0.4:1, healthy neuroretinal rim and attached retina in BE.Figure 1: Right eye showing superonasal diffuse avascular thin bleb (a). Left eye showing superonasal diffuse avascular thin bleb with scleral thinning, corneal vascularisation, and lipid deposits (b). Gonioscopy showing fistula with hyperpigmentation anterior to schwalbe's line at 2'0 clock (arrowhead) in the right eye (c) and increased pigmentation with prominent iris processes in the nasal quadrant in left eye (d). Ultrasound biomicroscopy image of the right (e) and left (f) eye showing communicating fistula between the anterior chamber and subconjunctival space, indicated by the arrowheadsCorneal topography was suggestive of oblique astigmatism with flattening along the meridian of the bleb without evidence of corneal ectasia in BE. Ultrasound biomicroscopy revealed a communicating fistula between the anterior chamber and subconjunctival space in BE [Fig. 1e and f]. Physical examination was unremarkable, except for depigmented patches in the skin. Blood investigations revealed high thyroid peroxidase antibody titer (157 IU/mL), whereas C-reactive protein, rheumatoid factor, and antinuclear antibody were within normal limits. Discussion Spontaneous filtering bleb is a rare condition, which can develop if a communicating fistula between the anterior chamber and subconjunctival space is established. Spontaneous filtering bleb has been reported in patients with Axenfeld syndrome,[1] Terrien marginal degeneration,[2] Traboulsi syndrome,[34] connective tissue diseases,[56] and without any ocular or systemic association.[27] Our patient with hypothyroidism and vitiligo, has scleral thinning and subconjunctival bleb in both the eyes. There were no signs of anterior segment abnormalities or facial dysmorphism. Considering the fact that our patient has 2 autoimmune systemic conditions, we postulate that the scleral thinning and spontaneous bleb formation could be due to autoimmune etiology. 2.1 Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients 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. 2.2 Financial support and sponsorship Nil. 2.3 Conflicts of interest There are no conflicts of interest.

Research progress of corneal neovascularization in herpes stromal keratitis

Herpes simplex virus (HSV) infection can cause inflammatory reactions and angiogenesis of the cornea, which significantly reduce corneal transparency. Herpes stromal keratitis (HSK) is an immune mediated disease caused by HSV infection, and is associated with inflammation and angiogenesis of the cornea. It is difficult to control HSK therapeutically. Repeated episodes of HSK can result in chronic inflammatory disease in the corneal stroma. Neovascularization plays a key role in the pathogenesis of HSK, so inhibiting the angiogenesis will help to control HSK disease. In this review, the pathomechanism of HSK is described. The roles of multiple cytokines and soluble mediators in corneal vascularization are discussed, and the potential ways of preventing and controlling corneal vascularization induced by HSK are summarized. (Chin J Ophthalmol, 2019, 55:956-960).

Activating mutations in discoidin domain receptor 2 cause Warburg‐Cinotti syndrome

AbstractPurposeIn 2006 Warburg et al. described a patient with blepharophimosis, corneal vascularization, retinal degeneration, deafness, loss of subcutanous tissue, flexion contractures of the fingers and acro‐osteolysis. Some years later Cinotti et al. reported a similar patient. In addition, we identified tree individuals from two different families with a similar clinical picture. In total, all six individuals from four different families were examined to identify the gene mutation associated with this diseaseMethodsExome sequencing was performed on affected individuals. Patient skin fibroblasts was obtained and examined using Elisa and Western blot analysis to determine levels of phosphorylated DDR2 and downstream effector proteins. Patient fibroblasts were also treated with Dasatabib, a protein kinase inhibitor affecting DDR2.ResultsWe found two recurrent de novo mutations in DDR2, p.Leu610Pro or p.Tyr740Cys, to be associated with the condition. Increased phosphorylation of DDR2 was found suggesting reduced receptor autoinhibition and ligand‐independent activation of the kinase. Dasatinib prevented DDR2 autophosphorylation. No effect of the mutations were found on the examined downstream effector proteins of DRR2.ConclusionWe found two recurrent, activating mutations in DDR2, p.Leu610Pro and p.Tyr740Cys, to be associated with this progressive fibrotic condition that we suggest to be called Warburgh‐Cinotti syndrome. In vitro dasatinib prevented autophosphorylation of DDR2 suggesting an approach to patient treatment.Reference et al. (2018): . The American Journal of Human Genetics. https://doi.org/10.1016/j.ajhg.2018.20.013.

Impact study of polarized light on the eye in a experimental model of dry eye disease

AbstractNow dry eye disease (DED) influences each tenth inhabitant of the planet. Current question of modern ophthalmology are the search for new therapies, one of which is the application of BIOPTRON‐PILER therapy.PurposeTo study of pathophysiological mechanisms of action and clinical efficacy of poly‐ and monochromatic BIOPTRON‐PILER‐light of dry eye disease.MethodsHere, we used rats with an experimental model of the dry eye induced by inflammation of eye anterior surface. BIOPTRON‐PILER therapy was performed using the red filter of the BIOPTRON (Bioptron AG, Zepter Group, Swiss) at 1 day after induction of DED. Only the right eye was treated from the distance of 30 cm for 3 min. Each animal received a course of treatment for 10 days.ResultsAre showed that a fluorescein test carried out immediately after alkali application and on 1, 5 and 10 days demonstrated a gradual increase in corneal epithelization and vascularization. We observed substantial and statistically significant increase of lacrimation in experimental rats on a 1 day after induction of inflammation compared to naïve animals. By the 7 day, the lacrimation decreased to a level with subsequent tendency to further decreased tear production. At the same time, there was no significant reduction in tear production on 7th day in a group of rats with the anterior surface inflammation that received polarized red light treatment, which may indicate a possible anti‐inflammatory effect of such treatment.ConclusionObtained evidence of the positive anti‐inflammatory effect of BIOPTRON‐PILER‐light in experimental model of the dry eye disease.

MiRNA profile in normal and aniridia conjunctival cells versus severity of aniridia‐associated keratopathy

AbstractPatients with congenital aniridia develop aniridia‐associated keratopathy (AAK), most of them exhibiting a similar disease mechanism namely haploinsufficiency of the PAX6 gene. The clinical onset and progression of AAK is quite diverse across patients. MiRNAs may act as regulatory elements affecting AAK progression. In mouse animal models the role of miRNAs controlling corneal vascularization has come into research focus. Interestingly, some of the miRNAs involved in neovascularization of the cornea, such as miR‐204, are regulated by PAX6 expression. The aim of this study was to identify deregulated miRNAs in conjunctival cells of AKK patients compared to unaffected controls, also in context with PAX6 haploinsufficiency. We further attempted to correlate miRNA expression with clinical severity of AKK (Staging ranging from 0 intact limbus, no pannus, clear cornea to 4 – end‐stage, thick, white, opaque vascularized pannus). We analyzed the miRNA expression profile in conjunctival cells of 20 patients with AKK and 20 age and sex matched controls using microarrays. We identified 10 down‐ and 11 upregulated miRNAs, including downregulated miR‐204‐5p and upregulated mir‐375. The latter miRNA has been reported to bind in PAX6 3′ UTR. Two patients showed mir‐204‐5p expression levels similar to healthy controls. These patients had mutations in PAX6 flanking genes likely affecting PAX6 regulatory regions and 0‐1 severity of AAK phenotype. Our results show strong expression changes in miRNA profile of Aniridia patients.

Optical Coherence Tomography Angiography Imaging to monitor Anti-VEGF treatment of Corneal Vascularization in a Rabbit Model

Optical coherence tomography angiography (OCTA) is a well-established non-invasive retinal vascular imaging technique. It has been recently adapted to image the anterior segment and has shown good potential to image corneal vascularisation. The purpose of the study is to evaluate the usefulness of OCTA to monitor regression of corneal vessels following anti-VEGF (vascular endothelial growth factor) treatment using a previously established corneal vascularisation rabbit model. The regression of vessels following the treatment with aflibercept and ranibizumab anti-VEGFs using both topical instillation and sub-conjunctival injection was quantified using OCTA and compared with ICGA (indocyanine green angiography). Overall vessel density measurements using OCTA showed good correlation (r = 0.988, p < 0.001) with ICGA, with no significant difference between the two treatment groups (p = 0.795). It was also shown that OCTA provided good repeatability outcomes of the quantitative measurements. Using Bland-Altman plots, vessel growth density values between anti-VEGF treatments were compared to control saline group. It was observed that aflibercept provided longer lasting effect than ranibizumab. We also observed that in both drugs, the topical route of administration topical provided longer regression outcomes compared to one-time sub-conjunctival injection. Thereby, with this pilot study, it was demonstrated that OCTA is a reliable imaging technique to follow-up and monitor corneal vascularisation and its treatment quantitatively.

Spontaneous regression of congenital corneal opacity.

To determine the incidence of spontaneous regression of congenital corneal opacity (CCO) and identify clinical factors associated with the regression. Medical records and anterior segment photographs were reviewed of 57 eyes in 35 patients with CCO that were not related to congenital glaucoma, tumors, infection, trauma, or metabolic disorders and were followed up without corneal transplantation for longer than one year at Seoul National University Hospital. Spontaneous regression of corneal opacity was defined as a decrease in corneal opacity significant enough for visual axis clearance. Data on demographics, systemic, and ocular characteristics were collected and compared between patients who had spontaneous regression of CCO and those who did not. Spontaneous regression of corneal opacity developed in 32 eyes (22 patients, 56.1%) out of 57 CCO eyes (35 patients) at the mean 8.2 ± 5.4 months of age (the median 6.7 months). Absence of combined ocular anomalies such as iris anomaly, lens opacity, and peripheral corneal vascularization was significantly associated with the regression of opacity. Corneal opacity can spontaneously regress in 56.1% of eyes with CCO during the first year of life. Careful follow-up with amblyopia management can be one of treatment options for CCO.

Validation of a clinical assessment tool for cicatrising conjunctivitis

PurposeThis study was designed to validate a semi-quantitative clinical assessment tool for cicatrising conjunctivitis (CC). MethodsFifty-five patients (109 eyes) with mucous membrane pemphigoid (MMP) and 31 patients (61 eyes) with Stevens-Johnson syndrome (SJS) were included. Three methods were used for validation: (1) comparison of inter- and intra-observer reproducibility for the components selected for the initial version of the tool, (2) quantitative measurement of the scarring component with a fornix depth measurer, compared with qualitative Tauber grading methodology, (3) the final version of the tool was compared with the published Sotozono SJS grading system. Main outcome measures included: inter- and intra-observer reproducibility, calculation of composite measures of scarring and morbidity, component redundancy, and correlation with other grading systems. ResultsInter- and intra-observer agreement was moderate-to-excellent for graded components of conjunctival hyperaemia, upper and lower symblepharon, upper and lower fornix depth, corneal vascularisation, and corneal opacity. There was poor-to-good agreement for limitation of motility which was rejected from inclusion in the final tool. Composite scores for scarring components and morbidity components showed good-to-excellent agreement and distribution of ocular disease severity. Analysis of the composite components showed no redundancy - all components contributed independently. Comparison with both Tauber and Sotozono grading methodologies showed good concordance. ConclusionsThis study has developed the first validated assessment tool applicable to causes of CC. The tool is concise and discriminates patients with varying disease severity. It measures both disease activity and severity and is suitable for clinical and research applications.

Evaluation of subjective symptomatology in patients with limbal stem cell deficiency

Introduction: Patients suffering from limbal stem cell deficiency have a variety of symptoms ranging from hard-to-heal epithelial defects and recurrent corneal erosions to corneal vascularization and conjunctivalization, reduced visual acuity, photophobia, foreign body sensation, tearing, blepharospasm, and recurrent episodes of pain. Aim: The aim of the present study is to evaluate subjective symptoms in patients with limbal stem cell deficiency. Materials and Methods: The study included 64 patients with limbal stem cell deficiency, whose subjective signs of pain, photophobia, redness, tearing were evaluated using a questionnaire. The results were processed with SPSS v. 20 for Windows using variation, comparison and correlation analyses. Results and Discussion: An important part of the discomfort of patients, regardless of the type of the illness, is the pain that affects their psycho-emotional state. The best pain response was found in eye diseases, wearing contact lenses, dry eye, iatrogenic factors and eye surgery. A significant part of the patients (61%) complained of photophobia in the absence of light or medium illumination. After being treated, the percentage dropped to 15.6%. In our sample, before treatment, 54.7% of the patients complained of moderate to severe redness. After the treatment, this number fell to 9.4%. In 59.4% of the individuals redness was missing or slightly present. Prior to treatment, the most severe redness was found in patients with chemical/thermal burns (44.4%) followed by those with injuries (34.5%). The appearance of secretion did not change significantly, which we think is due to the relocation of the patients from the group of those with a puruloid secretion to the previous group, that with the appearance of clear secretion only. Conclusion: The assessment of subjective symptomatology and visual function in patients with limbal stem cell deficiency showed that the greatest effect was observed in pain followed by photophobia, which was greatly reduced after treatment with amniotic membrane transplantation and the symptoms were minimized as well

Ocular findings and selected ophthalmic diagnostic tests in a group of young commercially available Guinea and Skinny pigs (Cavia porcellus).

The purpose of this study is to evaluate a group of young commercially available Skinny pigs, to gain information regarding ocular findings in this breed of guinea pig. Comparisons of ocular findings are to be made between Skinny pigs and haired guinea pigs. Ten haired guinea pigs and ten Skinny pigs were examined. A complete ophthalmic examination including Schirmer tear test-II (STT-II), phenol red thread test (PRTT), rebound tonometry with TonoVet PLUS, Fluorescein and Rose Bengal stain was performed. Microbiology swabs for aerobic bacterial growth were collected from conjunctiva of both eyes prior to the ophthalmic examination. The ophthalmic examination revealed seven abnormal ocular findings: trichiasis, mucopurulent discharge, hyperemia/chemosis of the conjunctiva, corneal fibrosis, corneal vascularization, and foreign body on the cornea or conjunctiva. Skinny pigs had a significantly higher amount of mucopurulent discharge (P=.0133) and a significantly higher STT-II (P<.001) than haired guinea pigs. Although not significant, trichiasis, keratitis with corneal vascularization, and foreign body presence were more common in Skinny pigs. Significantly more Skinny pigs had Pasteurellaceae isolated from their conjunctiva than haired guinea pigs (P=.0112). Antimicrobial susceptibility for the five Pasteurellaceae organisms isolated revealed susceptibility toward oxytetracycline, tobramycin, ciprofloxacin, and ofloxacin, whereas resistance was found toward erythromycin, trimethoprim-sulfamethoxazole, and moxifloxacin. Young Skinny pigs have a higher risk of Pasteurellaceae-associated conjunctivitis. Oxytetracycline, tobramycin, ciprofloxacin, and ofloxacin were identified as topical antibiotics that may be useful for Pasteurellaceae-associated conjunctivitis in Skinny pigs.

Short- and Long-Term Results of Xenogeneic-Free Cultivated Autologous and Allogeneic Limbal Epithelial Stem Cell Transplantations.

Purpose:To evaluate the short- and long-term success rates of xenogeneic-free cultivated limbal epithelial stem cell transplantation (CLET) for the treatment of limbal stem cell deficiency (LSCD).Methods:Thirteen patients with LSCD underwent an autologous (n = 9) or allogeneic (n = 4) CLET. The primary end point was to assess the long-term anatomical success rate of transplanted grafts at a follow-up of at least 3 years, in comparison with the short-term outcomes. Secondary end points involved reviewing functional improvement, patient-reported symptoms, and change in percentage area of corneal vascularization in both short-term and long-term.Results:The mean short- and long-term follow-up periods were 2.1 ± 0.38 years and 6.7 ± 1.81 years, respectively. The total anatomical success rate was 46.1% in the short-term, but it decreased to 23.1% in the long-term. A partial success rate of 30.8% was observed in both short- and long-term, and the failure rate increased from 23.1% to 46.1%. The mean percentage of vessel area decreased from 12.11% ± 5.29% preoperatively to 7.82% ± 6.70% in the short-term and increased to 8.70% ± 6.32% in the long-term. There was a significant improvement in best-corrected visual acuity (P = 0.044) in the short-term although not in the long-term (P = 0.865).Conclusions:This study shows that anatomical and functional success rates of CLET decrease over time. We believe that the decline of success is related to the extent of disease, cell origin, and lack of niche protection because subtotal LSCD and autologous donor cells confer a higher chance of success in the long-term.

Acanthamoeba keratitis in Australia: demographics, associated factors, presentation and outcomes: a 15-year case review.

To report the demographics, frequency of potential predisposing factors, presentation and outcomes of Acanthamoeba keratitis (AK) at a quaternary eye hospital in Sydney, Australia over a 15-year period. A retrospective review of all patients diagnosed with AK at the Sydney Eye Hospital, Sydney, Australia between January 2002 and December 2016 was conducted. A total of 52 patients with AK at the quaternary referral hospital in Sydney, Australia, between January 2002 and December 2016, were included. The most commonly documented potential predisposing factors were contact lens wear (83%) and organic trauma (10%) in the non-contact lens wearers. An initial misdiagnosis of herpetic eye disease was made in 37% of patients. The presenting clinical features in order of frequency included; punctate epitheliopathy in 65% (n = 34), perineural infiltrate 46% (n = 24), stromal infiltrates 46% (n = 24), anterior uveitis 39% (n = 20), epithelial defect 35% (n = 18), limbitis 31% (n = 16), pseudo-dendrite 19% (n = 10), and ring infiltrate 4% (n = 7). Twenty-seven of the patients completed their follow-up at the Sydney Eye Hospital, improving their vision from 1.02 logMAR at presentation to 0.57 logMAR at last follow-up. Thirty-nine complications developed in 32 eyes and included corneal scarring and vascularisation, three patients experienced recurrences of AK and one patient developed a late-onset scleritis. In Australia, AK occurred predominantly in contact lens wearers with typical clinical features including epitheliopathy and perineural infiltrates. The patient demographics, frequency of potential predisposing factors and clinical presentation of AK were similar to case series from the UK and New Zealand.

Methacrylated gelatin hydrogels as corneal stroma substitutes: in vivo study

Methacrylated gelatin (GelMA) hydrogels were prepared to serve as corneal stroma equivalents. They were highly transparent (ca. 95% at 700 nm), mechanically strong and withstood handling and had high human corneal keratocyte viability (98%) after 21 days of culture period. In order to test the in vivo performance of the cell free GelMA hydrogels a pilot in vivo study was carried out using eyes of two white New Zealand rabbits. Hydrogel was implanted in a mid-stromal pocket created and without suture fixation, and observed for 8 weeks under a slit lamp. No edema, ulcer formation, inflammation or infection was observed in both the control (sham) and hydrogel implanted corneas. Corneal vascularization on week 3 was treated with one dose of anti-VEGF application. Hematoxylin and Eosin staining showed that the hydrogel was integrated with the host tissue with only a minimal foreign body reaction. Results demonstrated some degradation in the construct within 8 weeks as evidenced by the decrease of the diameter of the hydrogel from 4 mm to 2.6 mm. High transparency, adequate mechanical strength, biocompatibility and well integration with the host tissue, indicates that this hydrogel is a viable alternative to the current methods for the treatment of corneal blindness and deserves testing on larger number of rabbits and more extensively using microscopy, histology and immune histochemistry.

Study of visual outcome in patients undergoing penetrating keratoplasty

Introduction: To study the visual outcome in patients undergoing penetrating keratoplasty (PK). Materials and Methods: This was a prospective interventional study concerning patients who underwent optical and therapeutic PK in Hamidia hospital Bhopal during a period of Dec 2016 to May 2108. Age, gender, eye, indication of PKP, and best-corrected visual acuity (BCVA) constituting the preoperative data were recorded in a predesigned proforma. Penetrating keratoplasty was performed using similar technique and patients were followed up till a period of 1 year and post operative complications were identified and managed accordingly. The outcome was assessed in terms of percentage improvement in logMAR visual acuity and the variables affecting the final visual outcome were studied. Results: Of the total 50 cases of penetrating keratoplasty that were analyzed 33 were done for therapeutic purposes and 17 were done for optical reasons. Mean recipient age was 39.88 years ±2.9 years, range 3-68. Follow up period was 1 year. The indications were therapeutic (34%), post traumatic or post infective corneal scarring (50%), previous graft failure (6%) and pseudophakic bullous keratopathy (4%). In optical PK, 62.5% recipient eyes showed good visual improvement (improvement of more than -0.8 log MAR). 21.8% eyes showed moderate visual improvement, and 15.6% eyes showed no visual improvement. In eyes with therapeutic PK, 46.7% showed good visual improvement, 13.3% moderate and 40% showed no visual improvement. Conclusion: Penetrating keratoplasty done for both optical and therapeutic indications resulted in fairly good visual outcome. The pre-operative host risk factors were associated with an increased probability of graft rejection. Careful workup of recipients for corneal transplantation with reference to local and systemic risk factors is of utmost importance in the outcome of corneal transplantation with regards to graft survival. Keywords: Corneal vascularisation, Graft failur

Differential effects of primary disease and corneal vascularisation on corneal transplant rejection and survival

AimsTo investigate the relative risk of pretransplant corneal vascularisation on rate of rejection and graft failure within 5 years of surgery when categorised by indication for transplantation.We analysed all adults...

This Issue of Acta

This Issue of Acta

Synthesis and Screening of Pro-apoptotic and Angio-inhibitory Activity of Novel Benzisoxazole Derivatives both In Vitro and In Vivo.

Triple Negative Breast Cancer (TNBC) tends to be more aggressive than other types of breast cancer. Resistance to chemotherapy is a major obstacle hence there is a significant need for new antineoplastic drugs with multi-target potency. Numerous Benzoisoxazole moieties have been found to possess a broad spectrum of pharmacological activities. In the present study, we have synthesized 9 novel derivatives of Benzisoxazole 7(a-i) and screened them for their biological potential. Chemical synthesis, Mass spectrometry (HRMS), cell proliferation and cytotoxicity assay, wound healing assay, flow cytometry and nuclear staining. Angio-inhibitory activity assessed by corneal micropocket assay and in vivo peritoneal angiogenesis assay. The Benzisoxazole derivatives 7(a-i) were synthesized and screened for their biological potency by both in vitro and in vivo experimental models. Among the series, compound 3-(1-((3-(3(Benzyloxy)-4-methoxyphenyl)- 4,5-dihydroisoxazole-5-yl)methyl)piperidine-4-yl)6-fluorobenzo[d] isoxazole (7e) was found to be most promising, with an average IC50 value of 50.36 ± 1.7 µM in MTT assay and showed 81.3% cell death. The compound 7e also showed 60-70% inhibition on a recombinant Metastasis-Associated protein (MTA1) induced proliferation and cell migration in MDAMB-231 cells, which is known to play a major role in angiogenesis. The anti-tumour studies inferred the regression of tumour activity. This was due to inhibition of neovascularization and evoking apoptosis process as assessed by corneal vascularization, peritoneal angiogenesis and apoptotic hallmarks in 7e treated cells. These findings not only show the biological efficacy of compound 7e but it is also an effective beginning to explore the mechanism of metastasis and cancer therapy strategy targeting MTA1. The observed biological activity makes compound 7e an attractive drug candidate.

Ocular mucous membrane pemphigoid: a review.

Ocular mucous membrane pemphigoid (MMP) is a rare, immuno-mediated chronic progressive condition of the conjunctiva characterized by blisters developing from sub-epithelial tissue through disruption of the adhesions between the conjunctival epithelium and the sub-epithelium. Patients with ocular MMP, in many cases, develop profound conjunctival scarring and visual impairment. Furthermore, ocular MMP may lead to a progressive secondary corneal vascularization and to corneal opacification. Ocular MMP is difficult to diagnose during the initial stages because of false negatives during biopsy and variability in the clinical presentation. Most of the current pharmacological treatments aim to control the inflammatory response to reduce the progressive tissue remodeling which leads to the formation of a fibrotic scar. The course and prognosis of ocular MMP depend on the severity and progression of the disease after systemic immunomodulatory therapy. The aim of this review is to provide a comprehensive analysis of the current literature on established and emerging concepts in ocular MMP, with special attention to its clinical presentation, diagnosis, treatment, and pathogenic mechanisms, including the role of some cytokines and growth factors in the development of thedisease.

Inflammation, vascularization and goblet cell differences in LSCD: Validating animal models of corneal alkali burns

Limbal stem cell deficiency (LSCD) is one of the serious cause of visual impairment and blindness with loss of corneal clarity and vascularization. Factors such as ocular burns (acids, lime, thermal), genetic disorders or infections results in the loss of limbal stem cells leading to LSCD. Reliable animal models of LSCD are useful for understanding the pathophysiology and developing novel therapeutic approaches. The purpose of the present study was to validate small and large animal models of LSCD by immunohistochemcal, clinical and histopathological comparison with human. The animal models of LSCD were created by topical administration of sodium hydroxide on the ocular surface of C57BL/6 mice (m, n = 12) and New Zealand white rabbits (r, n = 12) as per the standard existing protocol. Human corneal specimens (h, n = 12) were obtained from tissue bank who had chemical burn-induced LSCD. All samples were either paraffin embedded or frozen in cryogenic medium and the sections were processed for Hematoxylin-Eosin and Periodic Acid–Schiff staining to analyse the morphology and histopathological features of the corneal surface such as vascularization, inflammation, presence of goblet cells, epithelial hyperplasia and keratinization. Immunofluorescence was performed to distinguish between corneal (CK3+), conjunctival (CK19+) and epidermal (CK10+) epithelial phenotype. Histological analysis of corneal specimens from the three groups showed the presence of goblet cells (h:83%, m:50%, r:50%, p = 0.014), epithelial hypertrophy (h:92%, m:50%, r:66.6%, p = 0.04), epithelial hyperplasia (h:50%, m:17%, r:17%, p = 0.18), intra epithelial edema (h:42%, m:33%, r:100%, p = 0.02), stromal inflammation (h:100%, m:67%, r:67%, p = 0.01) and stromal vascularization (h:100%, m:50%, r:67%), in varying proportions. Immunostaining showed presence of total LSCD (CK19 + and/or CK10+, CK3-) in 92% of human and 50% of animal specimens. While partial LSCD (CK19 + and/or CK10+, CK3+) was seen in 8% of human and 50% of animal specimens. Our study shows the significant differences in the extent of vascularization, inflammation, epithelial thickness and goblet cell formation in mice and rabbit models of LSCD when compared to post-chemical burn LSCD in human corneas. In both mice and rabbit models complete LSCD developed in only 50% of cases and this important fact needs to be considered when working with animal models of LSCD.