Crosslinking-Induced Corneal Endothelium Dysfunction and Its Protection by Topical Ripasudil Treatment

Purpose. To investigate the changes of corneal endothelium under different crosslinking conditions and the protective effect of ripasudil. Methods. Corneal crosslinking groups were infiltrated with riboflavin and subsequently irradiated with 0.54 J/cm2 or 1.08 J/cm2 UVA, while noncrosslinking groups included neither UVA nor riboflavin treatment, only 1.08 J/cm2 UVA and only riboflavin treatment. Corneal opacity, variations in corneal endothelial cells, and corneal thickness of all groups were observed by slit lamp, in vivo confocal microscopy, and optical coherence tomography. Immunofluorescence staining and scanning electron microscopy were performed to evaluate changes in the structure and function of the corneal endothelium. The mice that received a corneal crosslinking dose of 1.08 J/cm2 were instilled with ripasudil to explore its protective effect on the corneal endothelium. Results. Treatment with UVA and riboflavin caused an increase in corneal opacity and corneal thickness and decreased endothelial cell density. Furthermore, treatment with UVA and riboflavin caused endothelial cell DNA damage and destroyed the tight junction and pump function of the endothelium, while riboflavin or the same dose of UVA alone did not affect the endothelium. Ripasudil reduced DNA damage in endothelial cells, increased the density of cells, and protected the endothelium’s integrity and function. Conclusion. Riboflavin combined with UVA can damage the corneal endothelium’s normal functioning. The corneal endothelium’s wound healing is dose-dependent, and the ROCK inhibitor ripasudil maintains the endothelium’s pump and barrier functions.

Possible association between viral infection and poor survival of the corneal graft after penetrating keratoplasty in patients with congenital corneal opacity: a cohort study

BackgroundCongenital corneal opacity (CCO) is a rare disorder. Penetrating keratoplasty (PK) is the main surgical option for CCO, but many factors affect graft survival. Therefore, this study aimed to perform a virological examination of CCO specimens after PK to explore the relationship between virological factors and graft survival after PK.MethodsThis prospective study included consecutive patients (<6 months of age) diagnosed with CCO and treated with PK at Beijing Tongren Hospital from August 2017 to January 2018. Next-generation sequencing was used to detect viral DNA in the CCO specimens. The survival of the primary graft was analysed using the Kaplan-Meier method.ResultsOverall, 24 eyes of 24 infants were treated with PK during the study period. The mean age at surgery was 4.8±1.1 months. Epstein-Barr virus DNA was detected in two specimens, varicella-zoster virus DNA in one specimen, herpes simplex virus DNA in three specimens and cytomegalovirus DNA in one specimen. In the virus-positive group, only one (14.3%) graft remained clear during follow-up. In contrast, in the virus-negative group (n=17), 13 (76.5%) grafts were still clear at the last follow-up. The mean survival of the grafts in the virus-positive group was significantly shorter than in the virus-negative group (11.0±9.8 months vs 27.1±7.7, p<0.001).ConclusionThe presence of viral DNA in CCO specimens might be associated with poor graft survival after PK.

Suppression of lipopolysaccharide-induced corneal opacity by hepatocyte growth factor

Keratitis induced by bacterial toxins, including lipopolysaccharide (LPS), is a major cause of corneal opacity and vision loss. Our previous study demonstrates hepatocyte growth factor (HGF) promotes epithelial wound healing following mechanical corneal injury. Here, we investigated whether HGF has the capacity to suppress infectious inflammatory corneal opacity using a new model of LPS-induced keratitis. Keratitis, induced by two intrastromal injections of LPS on day 1 and 4 in C57BL/6 mice, resulted in significant corneal opacity for up to day 10. Following keratitis induction, corneas were topically treated with 0.1% HGF or PBS thrice daily for 5 days. HGF-treated mice showed a significantly smaller area of corneal opacity compared to PBS-treated mice, thus improving corneal transparency. Moreover, HGF treatment resulted in suppression of α-SMA expression, compared to PBS treatment. HGF-treated corneas showed normalized corneal structure and reduced expression of pro-inflammatory cytokine, demonstrating that HGF restores corneal architecture and immune quiescence in corneas with LPS-induced keratitis. These findings offer novel insight into the potential application of HGF-based therapies for the prevention and treatment of infection-induced corneal opacity.

A Qualitative Study Using Semi-Structured Interviews: Comparing the Views of Palliative Care Unit Patients and Clinicians on Corneal Donation Discussions

Background: Blindness from corneal opacity accounts for 12% of cases of blindness worldwide. There is a severe shortage of corneas for donation worldwide for transplantation and research purposes. One group of individuals who could potentially be donors are those who die within the inpatient palliative care unit. The aims of the study were to 1. determine the frequency of corneal donation discussion; 2. determine whether inpatient palliative care unit patients and clinicians were aware of the potential for corneal donation discussions and 3. explore the attitudes and beliefs of inpatient palliative care unit patients and clinicians about corneal donation. Methods: An exploratory qualitative study was designed where inpatient palliative care unit patients and clinicians were invited to a semi-structured interview. A total of 46 face to face interviews were undertaken involving inpatient palliative care unit patients (20) and clinicians (26) in three major inpatient palliative care units in South Australia. Results: Very few patient participants were asked about corneal donations during their time in palliative care. Most inpatient palliative care unit clinicians did not bring up the topic as they felt other areas of care took precedence. Inpatient palliative care unit patients thought if inpatient palliative care unit clinicians did not raise the topic, then it was not important. Conclusions: Findings suggest that patients are receptive to discussing corneal donations, but few discussions are occurring. There were some differences between patient and clinician views, such as preference about who raises the possibility of donation and when the discussion might occur.

Opening a dacryocystorhinostomy into the opposite nasal cavity in a case of hemiarhinia

Heminasal agenesis is an exceedingly rare congenital anomaly which is frequently associated with disorders of eye, lacrimal drainage system and face. At times, a proboscis may also be noted with this condition. Herein, we present a case of a 13-year-old boy who presented to us with heminasal agenesis with concomitant microphthalmos, leucomatous corneal opacity, blepharoptosis, dacryocystocoele and maxillary hypoplasia. The child underwent a modified transeptal external dacryocystorhinostomy with placement of a lacrimal stent. There was significant improvement of epiphora and discharged following surgery. Heminasal aplasia with dacryocystocoele is surgical challenge; however, a well thought out surgical approach can yield satisfactory outcomes.

A Clinical Case of Two-Stage Visual-Functional Rehabilitation of a Patient with Postinfectious Central Corneal Opacity in Combination with Mixed Astigmatism Using Laser Keratorefractive Surgery

Introduction: to evaluate the clinical and functional results of two-stage treatment in a patient with post-infectious Central corneal opacity combined with mixed astigmatism.Patient and methods. Patient N., 19 years old with postinfectious (postherpetic) Central corneal opacity, mixed astigmatism was examined and operated using two-stage corneal laser treatment. To determine the possibility of surgical treatment of the patient, a complex of General ophthalmology was performed (checking visual acuity near and far in natural conditions and in conditions of drug-induced mydriasis, IOP measurement, autorefractometry, examination of visual fields, A- and Bscanning, ophthalmoscopy with examination of the Central and peripheral areas of the fundus), as well as special (keratopography and Scheimpflug camera examination, optical coherence tomography (OCT) of the anterior segment of the eye with analysis of the epithelial map, quantitative assessment (Schirmer test-1) and qualitative (tear film rupture time) lachrymal products, assessment of the epithelium state when stained with vital dyes and infrared meibography) research methods. To determine the activity of herpetic infection, PCR diagnostics were performed. The follow-up period was 2 years.Results and discussion. To achieve high visual-functional rehabilitation while preserving the native lens, a two-stage treatment algorithm was developed using technologies of laser corneal refractive surgery. At the first stage, in order to regularize the ocular surface and eliminate Central corneal opacity, an inverted topographically oriented PRK was performed; at the second stage, residual refractive errors were corrected using topographically oriented FemtoLASIK technology.Conclusion. According to the results of a literature search and analysis of Internet resources, there were no previously recorded and published works using a similar two-stage method. Therefore, the described clinical case justifies the relevance and novelty of the goal and has an evidence-based Foundation for the use of a two-stage laser keratorefractive treatment system in the ophthalmological practice of visual and functional rehabilitation of patients with Central corneal opacity in combination with mixed astigmatism or hypermetropic refraction. The two-year postoperative follow-up period showed stable and high visual-functional results with no recurrence of the inflammatory process.

Keratitis Treatment by Removal of Concealed Retrocorneal Plant Foreign Body

Purpose: We report a case of keratitis that improved after removal of a causative plant foreign body from below the posterior surface of an opaque cornea. The foreign body was revealed by anterior segment optical coherence tomography (AS-OCT) and gonioscopy.Case summary: A 79-year-old woman was referred with an impression of left-eye keratitis; the eye had been injured by a branch of a tangerine tree 1 month prior. She had been given the usual topical antibiotics by a local clinic, but they were ineffective. At her initial visit, her visual acuity was only hand motion in the left eye; slit-lamp examination revealed a 3 × 3-mm corneal infiltration with a hypopyon in the anterior chamber. Despite administration of strong topical antibiotics on an hourly basis, the corneal lesion worsened. AS-OCT and gonioscopy revealed a small foreign body below the posterior surface of the cornea; this was surgically removed. The corneal opacity and corneal epithelial defects dramatically improved, and the hypopyon disappeared.Conclusions: The possibility of a residual foreign body should be considered if trauma precedes infectious keratitis that does not improve with conventional treatment and the posterior surface of the cornea is not visible because of corneal opacity. In such a case, AS-OCT and gonioscopy can be useful.

The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.

Population-based study on the prevalence, clinical characteristics and vision-related quality of life in patients with corneal opacity resulting from infectious keratitis: results from the Corneal Opacity Rural Epidemiological study

AimTo estimate prevalence and characterise clinical features and vision-related quality of life (VR-QoL) of corneal opacities (COs) resulting from infectious keratitis in a rural North Indian population.MethodsThe Corneal Opacity Rural Epidemiological study was a cross-sectional study conducted in 25 randomly selected clusters of rural Gurgaon, Haryana, India to determine prevalence of corneal disease across all age groups. During house-to-house visits, sociodemographic details, presence, type and clinical characteristics of corneal disease, laterality and resultant visual impairment (VI) was noted. Subgroup analysis of data was performed to understand the prevalence, clinical characteristics, VR-QoL in patients with CO due to infectious keratitis. VR-QoL scores were compared with healthy controls.ResultsOverall, 65 of 12 113 participants had evidence of infectious keratitis-related CO with a mean age of 63.3 (±14.7 SD) years. Prevalence of infectious keratitis-related CO, including both bilateral (12/65) and unilateral (53/65) cases was 0.54% (95% CI 0.41 to 0.66) seen in a total of 77 eyes of 65 participants. Mean visual acuity was 1.18±0.80 with 30/77 (38.9%) eyes having a presenting visual acuity <3/60. Most of the CO due to infectious keratitis was <3 mm in size (61.03%; 47/77), nebular (42.85%; 33/77) and central (49.35%; 38/77) in location. These participants had significantly higher VR-QoL scores and hence poorer VR-QoL across all three domains of vision function (scores of 28 vs 22, 7.5 vs 5 and 15.5 vs 9, respectively; p<0.0001) when compared with healthy controls.ConclusionThe data from this study give an insight into the burden and clinical characteristics of COs resulting from infectious keratitis. VR-QoL is significantly impaired in patients with CO resulting from infectious keratitis, both in bilateral and unilateral cases.