High-risk Corneal Transplantation: Recent Developments and Future Possibilities.

Human corneal transplantation (keratoplasty) is typically considered to have superior short- and long-term outcomes and lower requirement for immunosuppression compared to solid organ transplants because of the inherent immune privilege and tolerogenic mechanisms associated with the anterior segment of the eye. However, in a substantial proportion of corneal transplants, the rates of acute rejection and/or graft failure are comparable to or greater than those of the commonly transplanted solid organs. Critically, while registry data and observational studies have helped to identify factors that are associated with increased risk of corneal transplant failure, the extent to which these risk factors operate through enhancing immune-mediated rejection is less clear. In this overview, we summarize a range of important recent clinical and basic insights related to high-risk corneal transplantation, the factors associated with graft failure, and the immunological basis of corneal allograft rejection. We highlight critical research areas from which continued progress is likely to drive improvements in the long-term survival of high-risk corneal transplants. These include further development and clinical testing of predictive risk scores and assays; greater use of multicenter clinical trials to optimize immunosuppressive therapy in high-risk recipients and robust clinical translation of novel, mechanistically-targeted immunomodulatory and regenerative therapies that are emerging from basic science laboratories. We also emphasize the relative lack of knowledge regarding transplant outcomes for infection-related corneal diseases that are common in the developing world and the potential for greater cross-pollination and synergy between corneal and solid organ transplant research communities.

Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of prematurity.

BACKGROUND: To describe outcomes in a cohort of extremely premature infants treated for aggressive posterior retinopathy of prematurity by diode laser panretinal photocoagulation. DESIGN: Retrospective study. PARTICIPANTS: Fifteen eyes in eight infants. METHODS: A review was carried out on infants between 23 and 25.6 weeks gestational age admitted to The Royal Brisbane and Women's Hospital neonatal intensive care unit between 1992 and 2009. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: Five hundred fifty-four infants were admitted to neonatal intensive care unit, 373 survived till screening, and 304 had retinopathy of prematurity. Sixty-six infants required treatment, and eight of these had aggressive posterior retinopathy of prematurity (2.5% of all infants with retinopathy of prematurity). Mean gestational age was 24.2 weeks, mean birthweight was 634 g, and treatment occurred at mean 34.1 weeks post-menstrual age. The mean total number of burns per eye was 2967. Five of 15 treated eyes required retreatment. Two patients subsequently died of unrelated causes. Regression occurred in 9 of 11 remaining eyes; one eye progressed to stage 4b and another to stage 5 retinopathy of prematurity. Vitrectomy was performed in two eyes. Five eyes had 6/12 vision, one had 3/60, and three had no perception of light. Of the remaining two eyes, one had good fixation and the other had poor fixation. CONCLUSIONS: Despite good structural outcomes, visual outcomes for conventional laser treatment of aggressive posterior retinopathy of prematurity are poor.

Unilateral optic neuropathy from possible sphenoidal sinus barotrauma after recreational scuba diving: a case report.

A case report is presented of a 35-year-old woman who developed a progressive right optic neuropathy while surfacing from a series of four recreational dives on the Great Barrier Reef, Queensland, Australia. The patient reported severe sudden onset blurred vision in the right eye associated with a mild headache and epistaxis on surfacing from diving. The patient had her first medical review the day after returning from her trip. At this time visual acuity in the right eye was 20/80, with left eye 20/20. There was a relative afferent pupillary defect in the right eye. A high-resolution computed tomography scan showed fluid in the right sphenoid sinus. Computed perimetry revealed patchy visual field loss in the right eye. The provisional diagnosis of sphenoidal sinus barotrauma-induced optic neuropathy was made. Over 10 days of observation, the visual acuity returned to 20/20 in the right eye and visual field changes resolved. This case highlights a very unusual cause of visual loss associated with diving.

Treatment of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the efficacy of laser diode therapy in the treatment of retinopathy of prematurity (ROP) in extremely premature (EP) infants over an 18-year period. DESIGN: Retrospective study. PARTICIPANTS: One hundred twenty-eight eyes in 66 infants treated between 23 and 25.6 weeks. METHODS: Five hundred fifty-four infants between 23 and 25.6 weeks gestational age (GA) were admitted to The Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit (NICU) between 1992 and 2009. Three hundred seventy-three patients survived to undergo screening, 304 were diagnosed with ROP, and 66 infants required diode laser therapy. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: One hundred twenty-eight eyes from 66 infants (18.8% of those screened) underwent laser treatment with a mean GA of 24.3 weeks and mean birth weight of 711.4g. Fifty-six eyes were treated at pre-threshold disease, and 72 eyes at threshold disease. Over the study period, the number of laser spots and regression rate of ROP increased, while the frequency of re-treatment decreased. At 40 weeks, 119 eyes had regressed ROP (93%), two advanced to stage 4a, three to stage 4b and four to stage 5. Aggressive posterior ROP (AP-ROP) occurred in 15 eyes (11.7% of those treated). Forty-three patients (65%) were followed up for a mean of 56.5 months. The number of laser spots correlated well with subsequent refractive error but poorly with corrected visual acuity. CONCLUSIONS: In EP infants, laser diode therapy is an effective technique to halt the progression of ROP in most cases. AP-ROP is uncommon, even in this subgroup of extremely premature infants.

Incidence of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the incidence of retinopathy of prematurity (ROP) in a subgroup of extremely premature infants admitted to an Australian tertiary centre over an 18-year period. DESIGN: Retrospective study. Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit. PARTICIPANTS: Five hundred and fifty-four infants admitted between 23 and 25.6 weeks gestational age (GA). METHODS: The 18-year study was divided into three 6-year periods for analysis: period 1 (1992-1997), period 2 (1998-2003) and period 3 (2004-2009). Infants were compared based on their week of GA and by the study period in which they were born. MAIN OUTCOME MEASURES: GA, birthweight, incidence and severity of ROP. RESULTS: Three hundred seventy-three (67.3%) infants survived until ROP screening, and 351 (63.4%) survived until discharge. ROP incidence increased from 78.2% in period 1 to 86.1% in period 3. Over the entire study, 90.5% of 23-week GA infants had ROP compared with 89.7% of 24-week GA infants and 76.1% of 25-week GA infants. Mean birthweight was significantly lower in infants with any ROP (725.1 g) and ROP of at least stage 3 (720.8 g) compared with infants without ROP (806.5 g) (P < 0.0001). Twenty-three-week GA infants had more severe ROP (28.6%) than 24 weeks (18.3%) and 25 weeks GA (11.9%). CONCLUSIONS: There has been increased survival and incidence of ROP in extremely premature infants over the past 20 years. Lower birthweight and GA are both associated with higher incidence and more severe ROP.

Specific amacrine cell changes in an induced mouse model of glaucoma.

BACKGROUND: To investigate retinal cell population changes under chronic elevated intraocular pressure in an inducible mouse model of glaucoma. METHODS: Chronic unilateral ocular hypertension was induced in 40 C57BL6/J mice by ablation of the limbal episcleral veins. After 5, 20, 40 and 60 days of elevated intraocular pressure, specific retinal cell types were identified and/or quantified by immunohistochemistry for protein kinase C α, glial fibrillary acidic protein, parvalbumin and calretinin. Apoptotic cells were identified by TUNEL and cleaved caspase-3 immunohistochemistry. RESULTS: Elevations in intraocular pressure in the range 22-30 mmHg were developed and sustained in mice for up to 60 days. Protein kinase C α immunoreactivity localized to bipolar cells was unchanged. We observed a rapid increase in glial fibrillary acidic protein expression in Müller cells and a progressive loss of parvalbumin-labelled ganglion cells. After 60 days of elevated intraocular pressure, calretinin-immunoreactive cell counts declined by 55.4% and 46.4% in the inner nuclear and ganglion cell layers, respectively. However, at all time points examined, the markers of cell death were only observed in the ganglion cell layer, not in the inner nuclear layer. CONCLUSIONS: In addition to ganglion cell death and reactive Müller cell changes, chronic experimental elevation of intraocular pressure alters calcium-binding protein immunohistochemistry in amacrine cells. However, these changes are not indicative of amacrine cell loss but may represent early indicators of cellular distress that precede physiological dysfunction or cell death.