Keratoconus,allergy, itch,eye‐rubbing and hand‐dominance

Background: One hypothesis for the pathogenesis of keratoconus includes teenage allergy, ocular itch and associated eye‐rubbing. Methods: This study examined the prevalence of these factors for teenage and adult patients. The results for a sample of 53 subjects with bilateral keratoconus were compared with those for a control sample of non‐keratoconus subjects, who also routinely wore RGP contact lenses. The strongest dominant hand and the eye with more advanced keratoconus were also determined, to examine for a relationship between them. Results: The keratoconic sample reported significantly higher levels of allergy, itch and rubbing as teenagers and as adults. However, all distributions were bimodal, consistent with the hypothesis that allergy, itch and rubbing are relevant in the pathogenesis of keratoconus only when the highest levels of these factors are present. For example, a significant relationship between the stronger dominant hand and the more advanced eye was evident only in subjects who reported the most severe rubbing. Conclusions: This finding adds weight to the circumstantial evidence that rubbing contributes to the pathogenesis of keratoconus. Low levels of teenage rubbing by some keratoconic subjects suggest a non‐rubbing pathogenesis and that emphasis on rubbing management is not warranted in these cases. However, high levels of adult rubbing reported by many keratoconic subjects indicate that the standard advice to avoid vigorous and prolonged rubbing is often not effective, even when repeated. There appears to be an indication for the need to improve the management of eye‐rubbing for some patients with keratoconus or at risk of developing this disease.     

N‐chlorotaurine and its analogues N,N‐dichloro‐2,2‐dimethyltaurine and N‐monochloro‐2,2‐dimethyltaurine are safe and effective bactericidal agents in ex vivo corneal infection models

Purpose: N‐chlorotaurine (NCT) and its analogues N‐monochloro‐2,2‐dimethyltaurine (NVC‐612) and N‐dichloro‐2,2‐dimethyltaurine (NVC‐422) are new anti‐infectives for topical treatment for conjunctivitis. The aim of this study was to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo. Methods: Corneal buttons were excised from porcine eyes. In 183 of the 229 corneas, erosion and artificial superficial stromal incision were induced. They were bathed in suspensions of Pseudomonas aeruginosa or Staphylococcus aureus for 24 hr at 37°C and incubated in solutions of the test substances at 37°C and pH 7.1. Subsequently, they were subjected to histology (n = 20) or homogenized followed by quantitative bacterial cultures (n = 209). Ocular irritation was tested using the EpiOcular? tissue system (MatTek Corporation). Results: Bacterial accumulations were detected histologically both on the corneal surface and also in the anterior third of the stroma of incised corneal buttons. All three test compounds at a concentration of 55 mm (equals 1% NCT) reduced the bacterial counts of P. aeruginosa and S. aureus by approximately 5 log10 after 60‐ and 120‐min incubation, respectively. Significant killing was observed as early as after 5‐min incubation. Also intrastromal bacteria were inactivated. In the EpiOcular? tissue model, NCT, NVC‐422 and NVC‐612 had no or very low potential to irritate corneal tissue. Conclusion: N‐chlorotaurine, NVC‐422 and NVC‐612 are non‐irritating in cornea and kill P. aeruginosa and S. aureus, even following penetration into the deeper corneal stromal layers.     

Depression and mortality in the visually‐impaired,community‐dwelling,elderly population of Quebec

Purpose: To assess the effect of visual impairment (VI) on the risk of depression or death in the community‐dwelling elderly population. Methods: A population‐based, retrospective fixed cohort study was conducted in the community‐dwelling elderly (age ≥ 65 years) outpatient population of Quebec. The cohort was assembled through the Quebec medical services database and consisted of the 5063 patients aged ≥ 65 years who received a diagnosis of VI during the years 2000–2004. The reference cohort consisted of 16 932 elderly subjects who were randomly selected among members of the public drug programme. The outcome variables were depression and death. The main independent variable was VI and covariates included age, gender, chronic disease score, fracture and diabetes. Results: Controlling for covariates, VI was associated with an increased risk of depression although the effect was not modified by severity (hazard ratio [HR] = 1.35, 95% confidence interval [CI] 1.10–1.66 for severe VI; HR = 1.35, 95% CI 1.09–1.69 for moderate VI). Visual impairment was associated with an increased risk of mortality; patients with moderate vision loss had a higher risk of death (HR = 1.70, 95% CI 1.55–1.87) than those with severe vision loss (HR = 1.34, 95% CI 1.21–1.48). Conclusions: Given the ageing of the population, VI in elderly subjects is becoming a public health concern. These findings enhance the need to detect and treat VI in order to improve the quality of life and to prevent premature mortality in the elderly population.     

Bilateral,simultaneous, uveitis‐associated pupillary membranes

A 48‐year‐old Caucasian man with an established diagnosis of pathological ankylosing spondylitis with cervical spinal fusion and a lengthy history of acute, recurrent, anterior uveitis presented with decreased vision in both eyes. Biomicroscopic examination revealed bilateral inflammatory pupillary membranes associated with anterior uveitis to be the source of the visual compromise. Aggressive topical anti‐inflammatory and mydriatic therapy did not break the pupillary membranes and the patient ultimately underwent surgical resection of the membranes in both eyes. Vision returned to normal in one eye and was only slightly reduced in the fellow eye after a prolonged post‐operative period involving multiple ophthalmic surgical procedures. This is the first reported case of bilateral, simultaneous uveitis‐associated pupillary membranes.     

Soft‐shell technique using Viscoat® and Healon®5: a prospective,randomized comparison between a dispersive‐viscoadaptive and a dispersive‐cohesive soft‐shell technique

Purpose: To compare the efficacy of the dispersive‐viscoadaptive soft‐shell technique using Viscoat^® and Healon^®5 to the dispersive‐cohesive soft‐shell technique in reducing corneal endothelial cell damage during cataract surgery. Methods: In this prospective randomized study, 207 eyes of 171 cataract patients underwent phacoemulsification using the dispersive‐viscoadaptive soft‐shell technique (V‐group, 102 eyes) with Viscoat and Healon5 or the dispersive‐cohesive soft‐shell technique (C‐group, 105 eyes) with Viscoat and a cohesive agent (Opegan‐Hi^®). Each group was divided into two subgroups depending on the amount of ultrasound (%Min) used during phacoemulsification. Corneal endothelial cell density was examined preoperatively and 3 months postoperatively. The endothelial cell loss was compared between the two groups, and also between the subgroups. Results: The mean endothelial cell loss 3 months after surgery was 8.4 ± 5.6% standard deviation (SD) in the V‐group and 8.2 ± 6.2% in the C‐group (P = 0.787). In the subgroups with ultrasound of 10 %Min or less, the mean endothelial cell loss 3 months after surgery was 6.6 ± 4.6% in the V‐group and 5.5 ± 5.0% in the C‐group (P = 0.104). In the subgroups with ultrasound of over 10 %Min, this value was 10.6 ± 6.3% in the V‐group and 11.9 ± 5.7% in the C‐group (P = 0.413). The correlation coefficient of the endothelial cell loss rate and %Min was 0.245 (P = 0.0129) in the V‐group and 0.501 (P < 0.0001) in the C‐group. Conclusion: The dispersive‐viscoadaptive soft‐shell technique is as effective as the dispersive‐cohesive soft‐shell technique in protecting corneal endothelial cells during phacoemulsification regardless of the amount of ultrasound energy used.     

VIP,PACAP‐38, BDNF and ADNP in NMDA‐induced excitotoxicity in the rat retina

Purpose:  To evaluate the effect of intravitreal injection of N‐methyl‐D‐aspartate (NMDA) on brain‐derived neurotrophic factor (BDNF), pituitary adenylate cyclase‐activating peptide‐38 (PACAP‐38), vasoactive intestinal peptide (VIP) and the VIP‐associated glial protein activity‐dependent neuroprotective protein (ADNP) in the rat retina. These elements have well‐documented neuroprotective properties and may thus be integrated in endogenous neuroprotective mechanisms in the retina which break down in NMDA excitotoxicity. Methods:  A volume of 2 μl of 100 nmol NMDA was intravitreally injected into one eye of rats, the untreated eye served as a control. Time‐dependent effects of NMDA on VIP, PACAP‐38 and BDNF were detected by radioimmunoassay and ELISA, and the effect on the expression of VIP, PACAP‐38 and ADNP was evaluated by quantitative RT‐PCR 20 days after NMDA injection. Topical flunarizine served to find out whether the effect of NMDA is counteracted. Results:  Compared to PACAP‐38, VIP levels significantly decreased on days 1, 7, 14, 28 and 56 after NMDA injection indicating that VIPergic cells are more vulnerable than PACAP‐38‐expressing cells. The expression of VIP and ADNP but not of PACAP‐38 was found to be reduced, and application of topical flunarizine counteracted the decrease of VIP. BDNF levels significantly increased after days 1 and 3. Conclusion:  The early upregulation of BDNF seems to act neuroprotectively and leads to a delay of ganglion cell loss. Although there is no direct evidence, the decrease of VIP and ADNP – the consequence of the presence of NMDA receptors on these peptide‐expressing cells – might contribute to the breakdown of endogenous neuroprotective mechanisms given that the decrease of the VIP‐related ADNP runs in parallel with the decrease of VIP. Activating and maintaining these mechanisms must be the primary aim in the therapy of diseases with retinal neuronal degeneration.     

Anti‐aquaporin‐4 antibody‐positive optic neuritis

Purpose: It has recently been reported that the anti‐aquaporin‐4 antibody (AQP4‐Ab) can be a specific marker of neuromyelitis optica. We present three cases of optic neuritis (ON) where the patients tested positive for AQP4‐Ab, but showed no neurological signs. Methods: Sera were obtained from 32 Japanese patients with ON and no other neurological abnormalities (mean age 46 ± 20 years). AQP4‐Ab was detected by indirect immunofluorescence staining using human‐AQP4‐transfected HEK 293 cells. Results: AQP4‐Ab was positive in three female patients (aged 9, 64 and 82 years). Their illness was characterized by bilateral severe optic nerve involvement, insufficient visual recovery, and autoimmune abnormalities (such as positive antinuclear antibody). Two of these patients experienced recurrent episodes of ON. In at least two episodes, the intracranial portion of the optic nerve showed significant inflammation on magnetic resonance imaging. Conclusions: These cases indicate that some ON patients have an immunological pathogenesis similar to that seen in neuromyelitis optica. In addition, examination for AQP4‐Ab positivity in the initial phase of ON is important in predicting the prognosis, including the possibility of the development of transverse myelitis.     

Re‐examination of organ‐cultured,cryopreserved human corneal grafts after 27 years

Purpose: To determine the long‐term fate of cryopreserved corneas. Review of 17 organ‐cultered cryopreserved corneas grafted in 1978–1979. Methods: We measured visual acuity and refraction and performed biomicroscopy, applanation tonometry and optical pachometri (CCT). Endothelial photos were taken, cells were counted and morphology was studied. Results: Four of 16 grafted corneas were still clear after 27 years. Mean CCT was 0.52 mm, endothelial cell density was 882 cells/mm² and visual acuity was 0.25 or better with an average of 0.6 in the four patients. Cell morphology showed irregularity in shape and size. Conclusion: This study shows that cryopreserved endothelium can function as well as non‐frozen corneas and that a regular hexagonal pattern is not essential for corneal clarity. The four grafts showed long‐term durability despite the irregularity in shape and size.     

Neuroprotective effect of epigallocatechin‐3‐gallate against N‐methyl‐D‐aspartate‐induced excitotoxicity in the adult rat retina

Purpose: Epigallocatechin‐3‐gallate (EGCG), the major polyphenol of green tea, has been suggested to reduce glutamate excitotoxicity. We therefore investigated the potentially protective effects of EGCG against N‐methyl‐d ‐aspartate (NMDA)‐induced excitotoxicity in the retina. Methods: Female Wistar rats (n = 171) were divided into a normal control group (n = 9); saline control group with intravitreal saline injections (n = 54); NMDA control group with an intravitreal NMDA injection and intraperitoneal saline injections (n = 54); and NMDA study group (n = 54) receiving an intravitreal NMDA injection plus intraperitoneal EGCG (25 mg/kg) injections. Starting at 2 days prior to the intravitreal NMDA injection, the intraperitoneal injections were performed daily for the whole study period. At 12 hr, 1, 2, 3 days, 1 and 2 weeks after the intravitreal NMDA injection, the animals were killed. We counted the neurons in the retinal ganglion cell layer (GCL) on histological sections, measured the thickness of Thy‐1 immunoreactivity and assessed the expression of Thy‐1 mRNA by real‐time polymerase chain reaction. Results: At all time‐points, GCL cell density, thickness of Thy‐1 immunoreactivity and expression of Thy‐1 mRNA were significantly (all p < 0.05) lower in the NMDA control group than in the NMDA study group, in which the parameters were significantly (all p < 0.05) lower than in the saline control group and the normal control group. In both groups with an intravitreal NMDA injection, GCL cell density, thickness of Thy‐1 immunoreactivity and expression of Thy‐1 mRNA decreased significantly with increasing follow‐up time. Conclusions: Intraperitoneal application of EGCG resulted in a significantly less marked NMDA‐associated loss of retinal ganglion cells.