Corneal ring infiltrate- far more than Acanthamoeba keratitis: review of pathophysiology, morphology, differential diagnosis and management.

OBJECTIVE: Ring infiltrates usually accompany numerous infectious and sterile ocular disorders. Nevertheless, systemic conditions, drugs toxicity and contact lens wear may present with corneal ring infiltrate in substantial part. Considering its detrimental effect on vision, detailed knowledge on etiology, pathophysiology, differential diagnosis, and management should be considered essential for every ophthalmologist. METHODS: The PUBMED database was searched for "corneal ring infiltrate" and "ring infiltrate" phrases, "sterile corneal infiltrate" and "corneal infiltrate". We analyzed articles written in English on risk factors, pathophysiology, clinical manifestation, morphological features, ancillary tests (anterior-segment optical coherence tomography, corneal scraping, in vivo confocal microscopy), differential diagnosis and management of corneal ring infiltrate. RESULTS: Available literature depicts multifactorial origin of corneal ring infiltrate. Dual immunological pathophysiology, involving both antibodies-dependent and -independent complement activation, is underlined. Furthermore, we found that the worldwide most prevalent among non-infectious and infectious ring infiltrates are ring infiltrates related to contact-lens wear and bacterial keratitis respectively. Despite low incidence of Acanthamoeba keratitis, it manifests with corneal ring infiltrate with the highest proportion of the affected patients (one third). However, similar ring infiltrate might appear as a first sign of general diseases manifestation and require targeted treatment. Every corneal ring infiltrate with compromised epithelium should be scraped and treat as an infectious infiltrate until not proven otherwise. Of note, microbiological ulcer might also lead to immunological ring and therefore require anti-inflammatory treatment. CONCLUSION: Corneal ring infiltrate might be triggered not only by ocular infectious and non-infectious factors, but also by systemic conditions. Clinical assessment is crucial for empirical diagnosis. Furthermore, treatment is targeted towards the underlying condition but should begin with anti-infectious regimen until not proven otherwise.

Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study.

PURPOSE: Animal studies suggest that gut bacteria metabolites are involved in regulation of intraocular pressure or development of glaucoma. However, clinical data are lacking. Here, we wanted to compare level of trimethylamine (TMA), an uremic toxin produced by gut bacteria, along with betaine and trimethylamine N-oxide (TMAO), a substrate and a product of its metabolism, in the aqueous humor and in plasma of patients with glaucoma and their controls. METHODS: Twenty patients were selected for cataract phacoemulsification, and 20 patients selected for phacotrabeculectomy were enrolled in the study. Patients were matched with controls on systemic diseases and estimated glomerular filtration rate. Blood samples were collected in the preoperative suite, whereas aqueous humor samples were collected as the first step of both procedures. Subsequently, level of betaine, TMA and TMAO was analyzed by means of chromatography. RESULTS: In the aqueous humor, level of TMA, but not betaine or TMAO, was significantly higher in the phacotrabeculectomy group than in the phacoemulsification group. Plasma level of betaine, TMA and TMAO was similar between groups. In both groups, level of betaine and TMA, but not TMAO, was significantly higher in plasma than in the aqueous humor. CONCLUSION: TMA, but not TMAO or betaine level, is increased in the aqueous humor of patients with glaucoma. TMA might play a role in pathogenesis of glaucoma; however, prospective studies are needed to confirm our findings.

Occurrence of viral DNA in paired samples of corneal rim and cornea preservation fluid.

Corneal transplants have one of the highest success rates among all transplantological procedures. Corneas intended for transplantation are stored in a preservation fluid, which is then tested for bacterial and fungal infections. Among all analyses of infectious complications following corneal transplants, infections caused by bacteria or fungi are the most prominent. Surprisingly, however, apart from a few publications, there is a lack of data regarding the occurrence of viruses in donor corneas and the risk of transmitting these to their recipients. The intention of this research was therefore to determine the frequency with which human herpesvirus 1 (HHV-1), human herpesvirus 2 (HHV-2), and human adenovirus (HAdV) occur in transplanted corneal tissue, as well as in samples of preservation fluid. The study comprised 57 paired samples, with each pair consisting of a fragment of the corneal tissue remaining after its trepanation for transplantation surgery and a sample of corneal preservation fluid. Sample pairs were all tested for the presence of the DNA of three viruses (HHV-1, HHV-2, and HAdV) using real time PCR technique. Viral DNA was found in three of the tested corneas-HHV-1 DNA in one paired sample (1.8%) and adenovirus DNA in two single samples (3.5%). We postulate that virological testing of corneas for transplantation should be considered, particularly in the case of donors with increased risk factors for herpesvirus and adenovirus reactivation. J. Med. Virol. 89:732-736, 2017. © 2016 Wiley Periodicals, Inc.

Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy.

The product of the LIG3 gene encodes DNA ligase III, which is involved in the repair of oxidatively damaged DNA in the base excision repair pathway. We hypothesized that polymorphism in this gene may change susceptibility to oxidative stress and predispose individuals to the development of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Therefore, we investigated the association between genotypes and haplotypes of the g.29661G>A polymorphism (rs1003918) and the g.29059C>T polymorphism (rs1052536) of the LIG3 gene and the occurrence of KC and FECD in patients with FECD (258 individuals) or KC (283) and ethnically matched controls (300). The A/A genotype and the A allele of the g.29661G>A polymorphism were associated with increased occurrence of KC, while the G allele of this polymorphism was positively correlated with a decreased occurrence of this disease. The T/C genotype of the g.29059C>T polymorphism was associated with decreased FECD occurrence. In addition, the AT haplotype was associated with increased occurrence of KC and FECD, while the GT haplotype was associated with decreased occurrence of these diseases. The g.29661G>A and g.29059C>T polymorphisms may play a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.

Mutagenesis of mitochondrial DNA in Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is an age-related, slowly progressive disease, which may lead to loss of vision resulting from apoptosis of corneal endothelial (CE) cells, dysfunction of Descemet membrane (DM) and corneal edema. A growing body of evidence suggests that oxidative stress may play a major role in the pathogenesis of FECD and that mitochondria of CE cells are its main target. Mitochondrial DNA (mtDNA) is particularly prone to oxidative stress and changes in mtDNA were reported in FECD patients. In the present work we studied mtDNA damage and repair, mtDNA copy number, and the 4977bp common deletion in mtDNA in DM cells and peripheral blood lymphocytes (PBLs) isolated from FECD patients. PBLs from 35 FECD patients and 32 controls were challenged for 10min with hydrogen peroxide at 20µM and then left in a fresh medium for 3h, resulting in a decrease in mtDNA copy number in both groups. Damage to mtDNA was not fully repaired after 3h and the extent of remaining lesions was significantly higher in the patients than the controls. We observed a higher copy number and an increased extent of mtDNA damage as well as a higher ratio of the common 4977bp deletion in DM cells of FECD patients than the controls. Our results confirm that mutagenesis of mtDNA may be involved in FECD pathogenesis and disturbance in mtDNA sensitivity to damaging agent as well as changes in mtDNA damage repair along with alternations in mtDNA copy number may underline this involvement.

The role of the 148 Asp/Glu polymorphism of the APE1 gene in the development and progression of primary open angle glaucoma development in the Polish population.

Glaucoma is an ocular disorder that is characterized by progressive degeneration of the optic nerve and loss of visual field (VF). Recent data have suggested that the level of oxidative DNA damage in human trabecular meshwork is significantly increased in glaucomatous patients as compared to controls. It was also noted that progressive loss of visual field may by connected with elevated levels of oxidative DNA lesions. This hypothesis may suggest the role of an inefficient base excision repair pathway in primary open angle glaucoma (POAG) pathogenesis. The aim of the study was to evaluate the association of the 148 Asp/Glu APE1 gene polymorphism with the risk of POAG development. One hundred fifty patients with POAG and 190 controls were enrolled in our study. Gene polymorphisms were analyzed by PCR-CTPP. We did not observe a statistically significant difference between the frequencies of alleles and genotypes of the 148 Asp/Glu APE1 gene polymorphism in POAG patients and controls. However, the presented study indicated that 148 Asp/Glu of the APE1 gene was associated with decreased risk of progression of POAG with reference to the parameter VF. We suggest that the 148 Asp/Glu APE1 gene polymorphism may decrease the risk of POAG progression.

Clinical and microbiological efficacy of levofloxacin administered three times a day for the treatment of bacterial conjunctivitis.

PURPOSE: This randomized, investigator-masked study aimed to compare the clinical and microbiological effectiveness of three times daily administration of levofloxacin 0.5% eyedrops with the classic, more frequent dosing in patients with bacterial conjunctivitis. METHODS: A total of 120 patients with symptoms of bacterial conjunctivitis were enrolled. The patients were randomly assigned to receive 0.5% levofloxacin eyedrops three times daily to each eye for 5 days (experimental dosage group), or every 2 hours on days 1 and 2, and then every 4 hours on days 3-5 (up to four times per day) (classic dosage group). Ocular symptoms and signs were assessed on day 1, days 3 to 4, and 7 +/- 1 visits. Conjunctival cultures were obtained at baseline and final visits. Clinical outcomes were based on resolution of cardinal signs. Microbial outcomes were based on culture results. RESULTS: Eighty-six patients (41 experimental dosage, 45 classic dosage) were evaluated. There was no difference between the groups in frequency of patients with clinical outcome resolved (85.4% in experimental vs 93.3% in classic dosage group, p=0.3). The microbial eradication rates did not differ statistically between the groups (92.7% vs 95.6%, respectively, p=0.67). CONCLUSIONS: There was no statistically significant difference in the efficacy or safety between the two methods of drug administration. Analysis of the results of compliance supported our conclusion that the less frequent method of dosing of 0.5% levofloxacin eyedrops was more convenient for patients and resulted in better adherence to the drug-dosing scheme.

In vivo confocal microscopy of corneal grafts shortly after penetrating keratoplasty.

PURPOSE: To describe the microstructural status of corneal grafts shortly after penetrating keratoplasty (PK) and to evaluate the efficacy and safety of confocal microscopy in examining corneal grafts at that time. METHODS: A confocal microscope with a 40 x front lens was used to examine corneal grafts in 32 patients (32 eyes) 4 days after PK. Images were analyzed, and endothelial cell density counts were compared with presurgical, eye bank values determined by specular microscopy. RESULTS: Microstructural alterations of the graft included epithelial and stromal edema, epithelial degeneration in both superficial and basal cell layers, dark stromal striae, activated keratocytes, and needle-like structures in the stroma. Descemet membrane folds were visible in 31 of 32 grafts; in 1 graft, the dense stromal edema did not allow imaging of posterior layers. Stromal nerve fibers were imaged in 28 grafts (88%). Endothelial cell density ranged from 1666 to 2548 cells/mm2 (mean+/-SD, 2125+/-283 cells/mm2); perioperative endothelial cell density loss varied from 0% to 29% (mean, 12%). No adverse reactions or signs of worsening of clinical condition were observed after the examination. CONCLUSIONS: White light scanning slit confocal microscopy permits imaging of a graft's microstructure (including epithelium and stromal layers), as well as calculation of endothelium cell density, as soon as 4 days after PK. The most frequently observed morphologic alterations of corneal grafts shortly after PK include epithelial and stromal edema, epithelial degeneration, stromal striae, and Descemet membrane folds. Stromal nerves can still be seen in the graft 4 days after PK.