Paulo E. Stanga

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task

Background/aims To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. Methods High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19″ (48.3 cm) touch screen monitor located 12″ (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. Results Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. Conclusion In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss

Background Retinal prosthesis systems (RPS) are a novel treatment for profound vision loss in outer retinal dystrophies. Ideal prostheses would offer stable, long-term retinal stimulation and reproducible spatial resolution in a portable form appropriate for daily life. Methods We report a prospective, internally controlled, multicentre trial of the Argus II system. Twenty-eight subjects with light perception vision received a retinal implant. Controlled, closed-group, forced-choice letter identification, and, open-choice two-, three- and four-letter word identification tests were carried out. Results The mean±SD percentage correct letter identification for 21 subjects tested were: letters L, T, E, J, F, H, I, U, 72.3±24.6% system on and 17.7±12.9% system off; letters A, Z, Q, V, N, W, O, C, D, M, 55.0±27.4% system on and 11.8%±10.7% system off, and letters K, R, G, X, B, Y, S, P, 51.7±28.9% system on and 15.3±7.4% system off. (p<0.001 for all groups). A subgroup of six subjects was able to consistently read letters of reduced size, the smallest measuring 0.9 cm (1.7°) at 30 cm, and four subjects correctly identify unrehearsed two-, three- and four-letter words. Average implant duration was 19.9 months. Conclusions Multiple blind subjects fitted with the Argus II system consistently identified letters and words using the device, indicating reproducible spatial resolution. This, in combination with stable, long-term function, represents significant progress in the evolution of artificial sight.

Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments

AIMS To determine the prevalence of polypoidal choroidopathy in consecutive patients presenting with large haemorrhagic and exudative neurosensory retinal and retinal pigment epithelial detachments (PEDs) of over 2 mm in diameter in the absence of drusen. METHODS 40 patients were identified over a 5 month period of which 29 had haemorrhagic detachments, and 11 had purely exudative detachments. All had indocyanine green (ICG) angiography, and the presence was sought of large blood vessels in the choroid associated with localised dilated terminals that filled slowly and leaked ICG. RESULTS In 34 cases (85%) there was an appearance consistent with previous descriptions of idiopathic polypoidal choroidal vasculopathy. Of the six without polypoidal lesions the disorder was attributed to choroidal neovascularisation in four, chorioretinitis in one, and a fibrovascular PED in one. Of those with polypoidal lesions 20 (65%) were female, the mean age was 65.4 years (range 44–88), and 25 (74%) were white, seven (20%) black, and two (6%) east Asian. Eight had a history of hypertension. Visual acuity varied from 6/6 to counting fingers in the involved eye (mean 6/24). Bilateral polypoidal choroidal lesions were demonstrated in 16 patients (47%). The predominant location for these lesions was the macular region in 23 patients (68%). Polypoidal vasculopathy was found in 16 patients (47%) who had a previous diagnosis of age related macular disease (AMD). No patients had evidence of intraocular inflammation. CONCLUSIONS In a largely white patient population a high proportion of patients with haemorrhagic and exudative PEDs has evidence of polypoidal lesions on ICG angiography.

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind

PURPOSE Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

X-linked retinoschisis: an update

X-linked retinoschisis is the leading cause of macular degeneration in males and leads to splitting within the inner retinal layers leading to visual deterioration. Many missense and protein truncating mutations have now been identified in the causative retinoschisis gene (RS1) which encodes a 224 amino acid secreting retinal protein, retinoschisin. Retinoschisin octamerises is implicated in cell–cell interactions and cell adhesion perhaps by interacting with β2 laminin. Mutations cause loss of retinoschisin function by one of the three mechanisms: by interfering with protein secretion, by preventing its octamerisation or by reducing function in the secreted octamerised protein. The development of retinoschisis mouse models have provided a model system that closely resembles the human disease. Recent reports of RS1 gene transfer to these models and the sustained restoration of some retinal function and morphology suggest gene replacement may be a possible future therapy for patients.

Initial experience with the Pascal photocoagulator: a pilot study of 75 procedures.

Background: The Pascal is a semiautomated photocoagulator that delivers a pattern array of multiple burns in a rapid predetermined sequence with a single foot pedal depression. Each burn is reduced to 10 or 20 ms to achieve this. The authors report their early experience with this system. Methods: 75 procedures done in 60 patients divided into four groups—group A, patients undergoing panretinal photocoagulation (PRP); group B, patients undergoing focal or modified grid macular laser; group C, patients undergoing macular grid and group D, patients undergoing retinopexy—were retrospectively studied. Results: 31/34 procedures in group A, 24/26 procedures in group B, 5/7 procedures in group C and all eight patients in group D had successful outcomes. Significantly higher powers were required with the Pascal than with conventional laser (p<0.001) in eyes that underwent PRP and focal/modified grid macular treatment with both systems. Single session PRP was successfully performed in five patients, and five were successfully treated with a macular grid using pattern arrays only. No adverse events were noted. Conclusion: Although the shorter pulse duration of the Pascal necessitates the use of a higher power, it is not associated with adverse effects. The results here suggest that the Pascal photocoagulator is safe and effective, and offer several potential advantages related to the brief exposure time.

Optical coherence tomography in photodynamic therapy for subfoveal choroidal neovascularisation secondary to age related macular degeneration: a cross sectional study.

Aims: To introduce new terminology and validate its reliability for the analysis of optical coherence tomography (OCT) scans, compare clinical detection of cystoid macular oedema (CMO) and subretinal fluid (SRF) with OCT findings, and to study the effect of photodynamic therapy (PDT) on the foveal morphology. Methods: Patients with subfoveal, predominantly classic choroidal neovascularisation (CNV) secondary to age related macular degeneration (AMD) undergoing PDT were evaluated with refraction protocol best corrected logMAR visual acuity (VA), slit lamp biomicroscopy, stereoscopic fluorescein angiography (FFA), and OCT. New terminologies introduced to interpret the OCT scans were: neuroretinal foveal thickness (NFT), bilaminar foveal thickness (BFT), outer high reflectivity band thickness (OHRBT), intraretinal fluid (IRF), subretinal fluid (oSRF), and vitreomacular hyaloid attachment (VMHA). Results: Fifty six eyes of 53 patients were studied. VA was better in eyes with a thinner outer high reflectivity band (OHRBT) (p = 0.02) and BFT (p = 0.05). BFT was less in eyes that had undergone a greater number of PDT treatments (p = 0.04). There was poor agreement between OCT and clinical examination in the detection of CMO and subretinal fluid (κ = 0.289 and κ = 0.165 respectively). To validate the interpretation and measurements on OCT, two groups of 20 scans were analysed by two independent observers. There was good agreement between the observers in the detection of IRF, oSRF, and VMHA (p<0.001). Measurements of NFT and BFT had a high reproducibility, and of OHRBT reproducibility was low. Conclusions: New terminology has been introduced and tested. OCT appears to be superior to clinical examination and FFA in the detection of CMO. In this study, better vision was associated with a thinner OHRBT and/or the absence of SRF giving insight into the biological effect of PDT.

Pain responses of Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation: Manchester Pascal Study, MAPASS report 2.

Aims To evaluate pain responses following Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation (PRP). Methods Single-centre randomised clinical trial. 40 eyes of 24 patients with treatment-naive proliferative diabetic retinopathy randomised to 20 and 100 ms PRP under topical 0.4% oxybuprocaine. A masked grader used a pain questionnaire within 1 h (numerical pain score (NPS)) and 1 month after treatment (numerical headache score (NHS)). Primary outcome measure was NPS immediately post-PRP. Secondary outcome measures were mean NHS scores and levels of photophobia reported within 4 weeks of primary PRP. Results Mean laser fluence was significantly lower using 20 ms PRP (4.8 J/cm2) compared to 100 ms PRP (11.8 J/cm2; p<0.001). Mean NPS scores for treatment were 2.4 (2.3) (mild) for 20 ms PRP group compared to 4.9 (3.3) (moderate) in 100 ms PRP group—a significant difference (95% CI 4.3 to 0.68; p=0.006). Mean NHS score within 1 month was 1.5 (2.7) in 20 ms PRP group compared to 3.2 (3.5) in the 100 ms PRP group (p<0.05). The median duration of photophobia after 20 ms PRP was 3 h, and significantly less compared to 100 ms PRP after which 72 h of photophobia was reported (p<0.001). Conclusions Multi-spot 20 ms PRP was associated with significantly lower levels of anxiety, headache, pain and photophobia compared to 100 ms single-spot PRP treatment. Possible reasons include lower fluence, shorter-pulse duration, and spatial summation of laser nociception with multi-spot Pascal technique.

Optos-guided pattern scan laser (Pascal)-targeted retinal photocoagulation in proliferative diabetic retinopathy

Purpose:  To investigate the clinical effects and safety of targeted pattern scan laser (Pascal) retinal photocoagulation (TRP) in proliferative diabetic retinopathy (PDR).

In Vivo Laser-Tissue Interactions and Healing Responses From 20- vs 100-Millisecond Pulse Pascal Photocoagulation Burns

OBJECTIVES To compare in vivo burn morphologic features and healing responses of Pascal 20- and 100-millisecond panretinal photocoagulation (PRP) burns in proliferative diabetic retinopathy. DESIGN Prospective randomized controlled trial with 24 eyes assigned to either 20- or 100-millisecond Pascal PRP. Fundus autofluorescence and Fourier domain optical coherence tomography (FD-OCT) were performed 1 hour and 2 and 4 weeks after treatment. Main outcome measures included burn morphologic features on FD-OCT and greatest linear diameter (GLD) of laser burns as evaluated in 6 standard Early Treatment of Diabetic Retinopathy Study photographic fields using autofluorescence. RESULTS The contemporaneous increase in autofluorescence is observed with increasing pulse duration. Differences in mean GLD between 100- and 20-millisecond burns were 63 mum at 1 hour and 198 mum at 4 weeks (P < .001 for both). At 4 weeks, all burns corresponded to defects at the junction of inner and outer segments of photoreceptors (JI/OSP) and apical retinal pigment epithelium. After 4 weeks, the GLD of 20-millisecond burns reduced significantly by 35% (P < .001), with no change in 100-millisecond burns. CONCLUSIONS All burns initially appear as equivalent square-edged, columnar foci of hyperreflectivity in the outer retina. Pascal 20-millisecond burns progressively reduce in size, and this suggests a novel healing response localized to the JI/OSP and apical retinal pigment epithelium. The higher-fluence 100-millisecond burns develop larger defects due to thermal blooming and collateral damage.