UVEITIS CAUSED BY TREATMENT FOR MALIGNANT MELANOMA: A CASE SERIES.

BACKGROUND/PURPOSE: To report the largest case series to date of uveitis occurring in association with immunomodulatory therapy for malignant melanoma. METHODS: A retrospective multicenter case review. Twenty-two patients with uveitis occurring in association with either immunotherapy or targeted immune therapy for malignant melanoma were identified. RESULTS: Of 22 patients, 11 had anterior uveitis in isolation. The remainder showed a variety of clinical features including panuveitis, ocular hypotony, papillitis, cystoid macular edema, and melanoma-associated retinopathy. Most patients responded well to treatment. CONCLUSION: We report the largest case series to date of patients with uveitis secondary to drug treatment for malignant melanoma. These cases are likely to increase in number in the future as newer immunomodulatory therapies for cancers are developed and the indications for these drugs increase. A dilemma arises when patients respond well to these drugs but develop vision-threatening side effects.

Moorfields technique of donor cornea mounting for femtosecond-assisted keratoplasty: use of viscoelastic in the artificial anterior chamber.

Appropriate mounting and cutting of the donor sclero-corneal cap is often cumbersome during femtosecond laser-assisted keratoplasty. The authors describe a technique for donor cornea femtosecond laser cutting using ophthalmic viscoelastic devices. The donor sclero-corneal cap is mounted on the artificial anterior chamber using a dispersive ophthalmic viscoelastic device instead of saline solution. The chances of artificial anterior chamber pressure loss, inadequate applanation, and fluid leaks are consistently reduced with the use of dispersive ophthalmic viscoelastic devices. The speed of donor femtosecond laser cutting is increased. The viscosity and elasticity of dispersive ophthalmic viscoelastic devices greatly assist the procedure with regard to ease of applanation, corneal endothelium protection, and decreased distortion of the applanated cornea.

A systematic review of the diagnostic accuracy of ocular signs in pediatric abusive head trauma.

TOPIC: To review systematically the diagnostic accuracy of various ocular signs for pediatric abusive head trauma (AHT). CLINICAL RELEVANCE: Intraocular hemorrhages (IOH), perimacular retinal folds, traumatic retinoschisis and optic nerve sheath hemorrhages have been reported as cardinal signs of AHT. The evidence base supporting the accuracy of this interpretation, however, has not been systematically reviewed. METHODS: A systematic keyword search of MEDLINE, EMBASE, and Evidence-Based Medicine Reviews was conducted for original studies reporting ocular findings in AHT. Articles were graded using a checklist for systematic reviews of diagnostic accuracy. RESULTS: The initial search yielded 971 articles, of which 55 relevant studies were graded, and 20 studies met inclusion criteria and were included in the review. The overall sensitivity of IOH for AHT was 75% and their specificity was 94%. Intraretinal hemorrhage at the posterior pole was the most common finding, although extensive, bilateral, and multilayered IOH were the most specific for AHT. Optic nerve sheath hemorrhages had a sensitivity and specificity for AHT of 72% and 71%, respectively. Traumatic retinoschisis and perimacular retinal folds were reported in 8% and 14% of AHT, respectively, but were not reported in other conditions. CONCLUSIONS: Prospective, consecutive studies confirm that IOH in infants-particularly bilateral, extensive, and multilayered-are highly specific for AHT. Optic nerve sheath hemorrhages are significantly more common in AHT than in other conditions, in autopsy studies. Traumatic retinoschisis and perimacular folds are present in a minority of AHT, but rarely seen in other conditions.

Evaluation of patient suitability for a retinal prosthesis using structural and functional tests of inner retinal integrity.

The purpose of this study was to assess inner retinal structure and function in patients with retinitis pigmentosa (RP) using optical coherence tomography (OCT) imaging of the retina, and electrical stimulation of the retina with a contact lens electrode. OCT images of 17 RP patients were acquired at the macula and at four quadrants of the peripheral retina in both eyes. Analysis was made of the residual inner retinal thickness and nerve fibre layer thickness in RP patients, and this was compared to normal controls. Eight of these patients further underwent contact lens electrical stimulation of one eye and thresholds for phosphene perception were obtained. OCT imaging showed a significant amount of inner retinal preservation in the peripheral retina and the macula of RP patients despite severe visual acuity and visual field loss. Phosphene thresholds were obtained across the range of pulse durations tested but were much higher than those obtained in normal controls. Phosphene thresholds in RP patients moderately correlated with inner retinal thicknesses as measured by OCT. Preservation of inner retinal structure in patients with RP and the responsiveness of these eyes to electrical stimulation suggest adequate inner retinal preservation for a retinal prosthesis to be successful.

Development of an extraocular retinal prosthesis: evaluation of stimulation parameters in the cat.

Electrical stimulation of the retina with extraocular electrodes is a new approach to developing a retinal prosthesis for blind patients. We have evaluated stimulus and electrode configurations for an extraocular retinal prosthesis (ERP). In anesthetized cats, ERP disc electrodes of 1 mm, 2 mm and 3 mm diameter were sutured to the sclera over the lateral globe. Electrically evoked potentials (EEPs) were recorded over the ipsilateral visual cortex, which resulted from the retinal stimulation of the ERP electrodes with a return electrode placed at the medial canthus. Square pulses, triangular pulses and the effects of dark adaptation and electrode size on the amplitude and thresholds for a cortical response were investigated. Square pulses were more effective than triangular pulses for stimulating the retina. Dark adaptation leads to a large increase in the threshold for retinal stimulation. There was no difference in the threshold for stimulation between electrodes of 1 mm and 3 mm diameter. Stimulation of the retina with extraocular electrodes elicits an EEP that is similar to that generated by retinal stimulation with intraocular electrodes. The use of square pulses is preferred to triangular pulses to minimize the peak current density at the electrode-tissue interface. As there is little difference in the threshold current for retinal stimulation with 1 mm or 3 mm electrodes, 3 mm electrodes are preferred as this will decrease the charge density at the active surface of the electrode.

Stimulation of the retina with a multielectrode extraocular visual prosthesis.

BACKGROUND: An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. METHODS: In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. RESULTS: Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. CONCLUSIONS: Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.

Evaluation of extraocular electrodes for a retinal prosthesis using evoked potentials in cat visual cortex.

OBJECTIVE: To assess the efficacy of a device using extraocular electrodes as a retinal prosthesis by evaluating the responses evoked in the visual cortex to electrical stimulation. METHODS: In anaesthetised cats, a lateral orbital dissection and ipsilateral parietal craniotomy was performed. Two extraocular retinal prosthesis (ERP) disc electrodes were sutured to the sclera on the lateral and superior aspects of the globe. Retinal stimulation was performed with charge-balanced constant-current pulses. Potentials evoked in the visual cortex were measured with a ball electrode placed on the lateral gyrus after removal of the dura. RESULTS: Stable attachment of the ERP electrodes to the globe was achieved with scleral sutures. Visual cortex responses were recorded with the electrodes in bipolar and monopolar configurations. The evoked response consisted of an early component with a peak around 8 ms, and a late component with a peak after 50 ms. Thresholds for evoking a response occurred at current intensities as low as 500 microA. Through extrapolation from evoked response amplitude data, thresholds as low as 300 microA were calculated. Cathodal monopolar stimulation demonstrated lower thresholds than anodal stimulation for evoking cortical responses. CONCLUSIONS: The ERP electrodes can be easily attached to the globe and are effective in electrically stimulating the retina, evoking responses in the primary visual cortex. Threshold charge-density was within safe limits for neural stimulation.

Feasibility of extraocular stimulation for a retinal prosthesis.

BACKGROUND: We present a new approach to developing a retinal prosthesis for blind patients based on extraocular stimulation of the eye with disc electrodes. METHODS: Experiments to assess the feasibility of using extraocular stimulation in a retinal prosthesis were carried out in anaesthetised adult cats (n=6). A craniotomy and lateral orbital dissection were performed. Ball or disc electrodes were placed on the posterior scleral surface of the eye after incision of the periorbita. Cortical potentials evoked by electrical stimulation with these electrodes were recorded at the primary visual cortex. The viability of adapting the Nucleus 24 auditory brainstem implant (ABI) as an extraocular retinal prosthesis was also investigated. RESULTS: Electrodes placed on the exterior of the eye could reliably evoke visual cortex responses for a variety of configurations. Threshold currents for eliciting an evoked response were lower than 100 microA with single pulses. Strength-duration curves and cortical activation maps were obtained for different stimulus paradigms. It was possible to excite the retina to evoke a cortical response using the electrodes and stimulus capabilities in a standard Nucleus 24 ABI. INTERPRETATION: It is possible to electrically stimulate the retina with electrodes placed in an extraocular location. Threshold currents required to elicit a response were low, and comparable to epiretinal implants. Prototype electrodes, and a potential implant, were found to be effective at retinal stimulation.

Surface stimulation of the brain with a prototype array for a visual cortex prosthesis.

We are developing a neural prosthesis to electrically stimulate the visual cortex to restore basic visual perceptions to blind patients. The effects on cortical excitation of different stimulus configurations using a prototype electrode array are presented. Cats underwent a bilateral craniotomy to expose the cortex. An array for brain stimulation was placed on the surface of the right hemisphere. Cortical stimulation was undertaken in a variety of configurations while measuring the evoked responses that propagated through transcallosal pathways, at a homologous region on the contralateral hemisphere. Cortical excitation elicited by stimulation with a particular paradigm could be assessed by measuring the spatial spread and amplitudes of evoked responses in the contralateral hemisphere. Results from this transcallosal model have allowed us to examine the spatial and amplitude effects of cortical stimulation with our prototype electrode array and will aid in developing a neuroprosthesis for blind patients.

An in-vivo paradigm for the evaluation of stimulating electrodes for use with a visual prosthesis.

BACKGROUND: Electrical stimulation of the visual cortex with surface electrodes is able to elicit basic visual perceptions in blind patients. The development of a visual prosthesis for the blind will require an in-vivo model for the optimization of cortical neurostimulation with multielectrode arrays. METHODS: In anaesthetized cats a bilateral craniotomy was performed and the dura was removed to expose the cerebral cortex. A prototype stimulating electrode array was placed on a gyrus in one hemisphere, and the transcallosal evoked response (TER) to cortical stimulation by this electrode array was recorded at a homologous region in the contralateral hemisphere. RESULTS: The stimulating electrode array elicited TER of short latency (6.9 ms) in the contralateral hemisphere. Bipolar stimulation of adjacent electrodes on the array evoked similar TER regardless of the polarity of stimulation. Electrodes spread apart on the array caused higher amplitude TER than electrodes placed close together. Multielectrode stimulation evoked lower amplitude TER than bipolar stimulation. CONCLUSIONS: This transcallosal model of cortical neurostimulation is a useful method to evaluate electrode arrays and stimulation techniques in the development of a visual prosthesis.