Penelope J. Allen

First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis

Retinal visual prostheses (“bionic eyes”) have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Trial Registration Clinicaltrials.gov NCT01603576

Endogenous endophthalmitis: 10-year experience at a tertiary referral centre

PurposeEndogenous endophthalmitis (EE) is a sight-threatening emergency and the aetiology is often multifactorial. Delayed diagnosis may exacerbate the poor visual prognosis. We describe the management and visual outcomes of EE presenting to a tertiary referral centre.Patients and methodsA prospective consecutive case series of 64 patients presenting with presumed EE from 1997 to 2007 to the Royal Victorian Eye and Ear Hospital were included. All data were collected in a standardized manner. Outcome measures included: visual acuity, microbial profiles, and vitrectomy rate.ResultsIn total, 64 cases of EE were identified over the study period with a mean age of 57.5 years, and 53.5% were male. Presenting acuities ranged from Snellen 6/6 to no perception of light (NPL). Identifiable risk factors were present in 78.1%, with the majority related to intravenous drug abuse. A 64.1% culture positivity rate was recorded. A vitrectomy rate of 57, 56, and 21% was recorded in documented bacterial, fungal, and no growth cases, respectively. Final Snellen acuities ranged from 6/6 to NPL. A total of 5 out of 64 eyes were enucleated, of which 3 identified Klebsiellaspecies. Better visual outcome was documented in fungal cases.ConclusionEE is a serious ocular condition and has a varied aetiology. Visual outcomes are often poor, irrespective of the method of management. Fungal aetiology often confers a better prognosis, and vitrectomy is advocated for bacterial proven cases.

A Wide-Field Suprachoroidal Retinal Prosthesis Is Stable and Well Tolerated Following Chronic Implantation

PURPOSE The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. METHODS A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. RESULTS The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. CONCLUSIONS A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.

Development of a surgical procedure for implantation of a prototype suprachoroidal retinal prosthesis

Current surgical techniques for retinal prosthetic implantation require long and complicated surgery, which can increase the risk of complications and adverse outcomes.

Three cases of post-traumatic endophthalmitis caused by unusual bacteria.

Three cases of post‐traumatic endophthalmitis caused by unusual bacteria are presented. The pathogens identified were: (i) Bacillus cereus and Citrobacter freundii; (ii) Pseudomonas fluorescens; and (iii) Chryseobacterium meningosepticum and Stenotrophomonas maltophilia. Two of these pathogens have not previously been reported to cause endophthalmitis. The available literature regarding the individual cases is summarized and a brief discussion of post‐traumatic endophthalmitis is presented, with reference to a recently published large series at the authors’ institution.

Analysis of the Arg345Trp disease‐associated allele of the EFEMP1 gene in individuals with early onset drusen or familial age‐related macular degeneration

Background: A single base change within the EFEMP1 gene has been associated with malattia leventinese and Doyne honeycomb retinal dystrophy, two dominantly inherited macular diseases with early onset drusen. The aim of this study was to determine whether the same disease allele was also associated with other forms of early onset drusen or familial cases of age‐related macular degeneration.

Endogenous endophthalmitis associated with intravenous drug abuse: seven-year experience at a tertiary referral center

Purpose: Intravenous drug use (IVDU) is a known risk factor for endogenous endophthalmitis. Endogenous fungal endophthalmitis (EFE) is emerging as a common problem among this community. We describe the management and visual outcomes of acute IVDU-associated EFE. Methods: A prospective consecutive case series of 19 patients presenting with presumed acute IVDU-associated EFE from 2001 to 2007 to the Royal Victorian Eye and Ear Hospital was included. All data were collected in a standardized manner. Outcome measures included visual acuity, microbial profiles, and vitrectomy rate. Results: Nineteen cases of IVDU-associated EFE were identified. Eight of these (42%) were men, and the mean age was 32.7 years (SD ± 8.0 years). Presenting visual acuity ranged from 6/6 to perception of light, with 58% having a visual acuity of 6/48 or less at presentation. Thirteen (68.4%) were culture positive with all cultures identifying Candida species, and 52.7% underwent vitrectomy. Fifty percent of subjects overall achieved a final visual acuity of 6/18 or better. Men demonstrated improved visual acuity when compared with women (P = 0.04). Age had no effect on final acuity. Conclusion: Intravenous drug use is a significant risk factor for developing EFE. Good visual outcomes can be achieved with early treatment, often with intravitreal therapy alone.

Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.

Purpose To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis. Methods Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue. Results All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses. Conclusions Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

Anaesthesia for Caesarean section with ketamine

Fifty healthy mothers, with normal placental function, were anaesthetised with ketamine for Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. Surgery was conducted in the lateral tilt position. Arterial blood samples were drawn from the mothers, and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. Results obtained were compared with those of a previous series anaesthetised with thiopentone, nitrous oxide, oxygen and muscle relaxants. Eight infants were clinically depressed, judged on the basis of their modified Apgar score 2 minutes after delivery. The average time to sustained respiration (TSR) was 58.1 seconds. The mean maternal pH and base excess values in the ketamine group were significantly greather than those reported after thiopentone anaesthesia. Mean Uv and Ua pH levels were also significantly higher after ketamine; in contrast, the average fetal base excess values did not differ from those obtained previously with thiopentone. The mean (Ma-Uv) and (Ma-Ua), pH gradients were 0.019 and 0.025 pH units greater respectively in the ketamine group compared to the thiopentone (P less than 0.005). The average (Uv-Ua) PO2 gradient was 3.4 mmHg less after ketamine anaesthesia (P less than 0.005). A significant inverse correlation was observed relating the I-D interval to the Ma and Ua pH values. Maternal arterial base deficit values appeared to increase with delay in delivering the fetus. Prolongation of the uterine incision to delivery (U-D) interval was associated with a decrease in Ua pH and base excess values. (Ma-Ua) pH and base excess gradients increased with lengthening of the U-D interval. No convincing evidence of awareness during anaesthesia was found during the study. Five patients, appeared to be hallucinated in the immediate post-anaesthetic period. Unpleasant dreams were reported in 5 instances. In this study ketamine appeared to be unassociated with significant biochemical asphyxia, but may have been responsible for some element of drug induced neonatal depression. In view of our own experience and that of other workers, it is suggested that ketamine induction for Caesarean section should be re-evaluated using a lower dose of the drug.

Wound‐related complications and clinical outcomes following open globe injury repair

Background Careful surgical management of traumatic wounds is important in open globe injury repair. This study examines the clinical outcomes following repair of open globe injuries with particular focus on wound-related issues. Design Retrospective, cohort study of consecutive open globe injuries presenting to a tertiary referral eye hospital from 1 January 2009 to 31 December 2011. Participants A total of 267 eyes of 263 patients, mainly male (82.5%) with a mean age of 44.8 (range: 4–97) years. Average follow up was 6.9 months. Methods All cases classified according to Ocular Trauma Classification Group. Main Outcome Measures Visual outcomes, risk factors for and rates of postoperative complications and endophthalmitis. Results There were 83 globe ruptures, 182 penetrating and 2 perforating eye injuries, of which 43 cases had intraocular foreign body. Factors contributing to final visual acuity (VA) <6/60 were poor presenting VA (odds ratio [OR] = 16.0, 95% confidence interval [CI]: 4.81–53.1), globe rupture (OR = 4.64, [1.99–10.8]), retinal detachment (OR = 3.40, [1.19–9.74]) and age ≥50 (OR = 2.45, [1.05–5.74]). Wound leak occurred in 44 eyes (16%). Of these, 18 (41%) proceeded to re-suturing. Factors contributing to wound leak were stellate-shaped wound (OR = 3.28, [1.39–7.73]) and delayed presentation (OR = 2.80, [1.02–7.71]). Ten eyes (3.7%) developed endophthalmitis. Factors associated with endophthalmitis were delayed presentation (OR = 8.91, [1.71–46.6]), microbial keratitis (OR = 12.5, [1.85–85.0]) and lens capsule breach (OR = 12.4, [1.85–83.1]). Conclusions Wound leak is an important postoperative complication of open globe injury repair. Delayed presentation is an important risk factor for postoperative wound leak and endophthalmitis. Prompt and meticulous wound management of open globe injury may reduce these complications.Careful surgical management of traumatic wounds is important in open globe injury repair. This study examines the clinical outcomes following repair of open globe injuries with particular focus on wound‐related issues.