Morphologic changes in the retina after selective retina therapy.

PURPOSE: To investigate structural changes in the retina by histologic evaluation and in vivo spectral domain optical coherence tomography (SD-OCT) following selective retina therapy (SRT) controlled by optical feedback techniques (OFT). METHODS: SRT was applied to 12 eyes of Dutch Belted rabbits. Retinal changes were assessed based on fundus photography, fluorescein angiography (FAG), SD-OCT, light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) at each of the following time points: 1 h, and 1, 3, 7, 14 and 28 days after SRT. BrdU (5'-bromo-2'-deoxy-uridine) incorporation assay was also conducted to evaluate potential proliferation of RPE cells. RESULTS: SRT lesions at1 h after SRT were ophthalmoscopically invisible. FAG showed leakage in areas corresponding to SRT lesions, and hyperfluorescence disappeared after 7 days. SD-OCT showed that decreased reflectivity corresponding to RPE damage was restored to normal over time in SRT lesions. Histologic analysis revealed that the damage in SRT lesions was primarily limited to the retinal pigment epithelium (RPE) and the outer segments of the photoreceptors. SEM and TEM showed RPE cell migration by day 3 after SRT, and restoration of the RPE monolayer with microvilli by 1 week after SRT. At 14 and 28 days, ultrastructures of the RPE, including the microvilli and tight junctions, were completely restored. The outer segments of the photoreceptors also recovered without sequelae. Interdigitation between the RPE and photoreceptors was observed. BrdU incorporation assay revealed proliferation of RPE on day 3 after SRT, and peak proliferation was observed on day 7 after SRT. CONCLUSION: Based on multimodal imaging and histologic assessment, our findings demonstrate that SRT with OFT could selectively target the RPE without damaging the neurosensory retina. Therefore, the use of SRT with OFT opens the door to the possibility of clinical trials of well-defined invisible and nondestructive retina therapy, especially for macular disease.

Optical Coherence Tomography Angiography in Macular Holes Autologous Retinal Transplant.

In this paper, we compare the post-operative macular microvascular parameters (vascular density and foveal avascular zone) in eyes with refractory macular hole (MH) that underwent pars plana vitrectomy and autologous retinal transplant (ART) with the fellow unoperated eye. We conducted a retrospective case control study of six consecutive patients who underwent pars plana vitrectomy and ART with at least six months of post-operative follow-up. Pre-operatively, all eyes underwent SD-OCT (Spectral Domain Optical Coherence Tomography) examination. Post-operative OCT-A analyses included vascular density (VD) and the foveal avascular zone (FAZ) area. Six patients with a mean age of 63.7 ± 14.3 years were included. The mean follow-up was 24 months (range 6-30 months). The pre-operative BCVA (best-corrected visual acuity) was 0.99 ± 0.46 logMAR and 1.02 ± 0.23 logMAR at the last post-operative visit (p = 1.00). The mean MH diameter was 966 ± 620 µm. VD in the MH group was 28.1 ± 7.3% compared to 20.2 ± 2.9% in the fellow eyes group (p < 0.05). The mean post-operative FAZ area in the MH group was 109.8 ± 114.6 mm2 compared to 41.5 ± 10.4 mm2 in the control group (p < 0.05). In all six eyes, MH closure was obtained. The post-operative visual acuity did not improve after ART. Eyes with a closed MH showed a bigger FAZ with a higher VD compared to the fellow healthy eye.

Exudative Retinal Detachment After ROP Laser Photocoagulation.

Exudative retinal detachment (ERD) can be a rare postoperative complication of laser photocoagulation surgery when used to treat type I retinopathy of prematurity (ROP). We present a case of bilateral ERD following ROP laser photocoagulation. A preterm male infant born at 24 weeks gestation and weighing 600 grams was diagnosed with stage 3/zone II/pre-plus ROP in both eyes. He was on oxygen therapy for 92 days due to chronic lung disease and was treated with laser photocoagulation at 40 weeks postmenstrual age. Initial laser settings (in use for over 15 years) were 300 mW power, 300 ms duration, and 300 ms intervals. Due to strong laser absorption, power was decreased to 250 mW for most of the procedure. He was prescribed prednisolone acetate drops four times per day for postoperative care. One week later, he developed complete ERD in both eyes. The patient was monitored in the neonatal intensive care unit (NICU) for three weeks and prednisolone acetate drops were increased to every two hours and tapered over one month. Complete resolution of ERD with residual peripheral exudate bilaterally was observed eight weeks after surgery. This case suggests that even after the settings of an ROP laser have been used safely for 15 years, it is important to tailor settings for each individual patient utilizing the least power and duration for laser application as possible. Furthermore, this case highlights the importance of titrating laser power in response to spot blanching throughout the procedure. However, near-complete resolution of post-ROP laser ERD is possible with minimal changes to standard postoperative management.

Autologous Neurosensory Retinal Transplantation: A Report of Three Cases.

PURPOSE: To present the anatomical and functional outcomes of autologous surgical transplantation of a free neurosensory retinal graft in three cases of recurrent and chronic full thickness macular hole (MH). METHODS: A retrospective case series, reporting the profile, preoperative presentation, surgical technique, and postoperative outcome of three consecutive eyes of three patients who had autologous retina transplantation (ART) surgery for recurrent and chronic MHs, and had a minimum of six months follow-up. The technique involved excision of a free neurosensory graft after laser demarcation of the harvest site. The graft was slid under perfluorocarbon liquid (PFCL) into the MH. A five-day tamponade with PFCL was used to secure the graft within the MH and then exchanged with air. RESULTS: The patients were one female and two males aged 60, 44, and 67 years, respectively. All eyes had successful surgery. Postoperative vision improved from 6/36 to 6/18 in patient 1 and remained same as preoperative vision in the other two eyes. No eye lost vision postoperatively. The main complication of surgery was occurrence of retinal and vitreous hemorrhage in one eye (this did not appear to jeopardize the outcome) and retraction of graft tissue in two eyes. CONCLUSION: ART appears to be a safe and effective treatment for difficult MHs. Our results are comparable to previous studies. Short-term use of PFCL can be useful to secure the graft within the MH. Methods of improving visual function should be the focus of further research in this promising area.

Optic nerve thinning and neurosensory retinal degeneration in the rTg4510 mouse model of frontotemporal dementia.

Visual impairments, such as difficulties in reading and finding objects, perceiving depth and structure from motion, and impaired stereopsis, have been reported in tauopathy disorders, such as frontotemporal dementia (FTD). These impairments however have been previously attributed to cortical pathologies rather than changes in the neurosensory retina or the optic nerve. Here, we examined tau pathology in the neurosensory retina of the rTg(tauP301L)4510 mouse model of FTD. Optic nerve pathology in mice was also assessed using MRI, and corresponding measurements taken in a cohort of five FTD sufferers and five healthy controls. rTg(tauP301L)4510 mice were imaged (T2-weighted MRI) prior to being terminally anesthetized and eyes and brains removed for immunohistochemical and histological analysis. Central and peripheral retinal labelling of tau and phosphorylated tau (pTau) was quantified and retinal layer thicknesses and cell numbers assessed. MR volumetric changes of specific brain regions and the optic nerve were compared to tau accumulation and cell loss in the visual pathway. In addition, the optic nerves of a cohort of healthy controls and behavioural variant FTD patients, were segmented from T1- and T2-weighted images for volumetric study. Accumulation of tau and pTau were observed in both the central and peripheral retinal ganglion cell (RGC), inner plexiform and inner nuclear layers of the neurosensory retina of rTg(tauP301L)4510 mice. This pathology was associated with reduced nuclear density (- 24.9 ± 3.4%) of the central RGC layer, and a reduced volume (- 19.3 ± 4.6%) and elevated T2 signal (+ 27.1 ± 1.8%) in the optic nerve of the transgenic mice. Significant atrophy of the cortex (containing the visual cortex) was observed but not in other area associated with visual processing, e.g. the lateral geniculate nucleus or superior colliculus. Atrophic changes in optic nerve volume were similarly observed in FTD patients (- 36.6 ± 2.6%). The association between tau-induced changes in the neurosensory retina and reduced optic nerve volume in mice, combined with the observation of optic nerve atrophy in clinical FTD suggests that ophthalmic tau pathology may also exist in the eyes of FTD patients. If tau pathology and neurodegeneration in the retina were to reflect the degree of cortical tau burden, then cost-effective and non-invasive imaging of the neurosensory retina could provide valuable biomarkers in tauopathy. Further work should aim to validate whether these observations are fully translatable to a clinical scenario, which would recommend follow-up retinal and optic nerve examination in FTD.

The Effect of Ranibizumab on Normal Neurosensory Retina in the Eyes of Patients with Exudative Age Related Macular Degeneration.

BACKGROUND: Anti-vascular endothelial growth factors have become the mainstay treatment for neovascular age related macular degeneration. Prolonged suppression of vascular endothelial growth factor raises concerns as it may result in harmful effects on retina. OBJECTIVE: The purpose of this retrospective chart review is to evaluate the 1-year effect of treatment with intravitreal injections of ranibizumab on normal neurosensory retinal tissue of patients with exudative age related macular degeneration using the Optical Coherence Tomography (OCT). METHOD: The study included sixty five eyes of 62 patients (32 male and 30 female; mean age 74.97±8.5 years) with exudative age related macular degeneration treated with intravitreal injections of ranibizumab with a pro re nata treatment regimen over a period of 1 year. The MM5 thickness maps acquired with the Optovue RTVue-100 Fourier-domain OCT at baseline, at 3 months, after the 3 loading doses of ranibizumab, and at the 1 year follow-up visit were used for analysis. Changes of inner and outer retinal thickness in four selected points of normal retina on the MM5 scan were evaluated. RESULTS: The patients received a mean of 6.4 ± 1.8 (median 6, range 3-11) intravitreal injections of ranibizumab over a period of 12 months. No significant change was observed in inner and outer retinal thickness at pre-selected spots of normal retina during the first year of intravitreal administration of ranibizumab. CONCLUSION: One year treatment with ranibizumab on an individualized, according to need dosing regimen does not seem to induce any detectable structural damage in the unaffected, normal retina.

Optical coherence tomography of the preterm eye: from retinopathy of prematurity to brain development.

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.