Bacillary layer detachment on optical coherence tomography in exudative age-related macular degeneration

Purpose To report the bacillary layer detachment on optical coherence tomography in exudative age-related macular degeneration. Methods Retrospective, observational cases Case descriptions Two cases of exudative age-related macular degeneration, one diagnosed as polypoidal choroidal vasculopathy following exudative age-related macular degeneration and other as wet age-related macular degeneration with choroidal neovascular membrane showed separation of myoid and ellipsoid zones of photoreceptor layer on optical coherence tomography. This is termed as BALAD. Other associated features noted were the presence of subretinal hyperreflective material, submacular hemorrhage and subretinal fluid. Both cases were treated with monthly intravitreal injections of Inj. Ranibizumab (0.5 mg/0.05 ml). Following 3 intravitreal injections at monthly intervals, reattachment of the bacillary layer detachment were noted in case 1 while the bacillary layer detachment persisted in case 2. Conclusion Multimodal imaging using optical coherence tomography in these cases revealed the separation of the bacillary layer following exudative age-related macular degeneration; a finding which is not routinely described in literature.

Early-stage macular telangiectasia type 2 vascular abnormalities are associated with interdigitation zone disruption

Purpose To investigate the relationship between disruption in different photoreceptor layers and deep capillary plexus (DCP) telangiectasias in eyes with macular telangiectasia type 2 (MacTel). Methods 35 eyes (21 patients) with MacTel imaged with optical coherence tomography angiography (OCTA) were included. Circumscribed areas of DCP telangiectasia were traced from OCTA slabs and the corresponding spectral-domain OCT (SD-OCT) slabs were used to visualize the photoreceptor layer interdigitation zone (IZ) and ellipsoid zone (EZ). IZ attenuation, IZ loss, and EZ loss were graded by reviewing en face SD-OCT slabs for hypo-reflective areas and confirming their status on cross-sectional views. Total area of photoreceptor disruption and overlap with DCP telangiectasia were evaluated with respect to OCT-based MacTel stage. Longitudinal changes were evaluated in a subset of patients with follow-up imaging. Results Overlap of DCP telangiectasia with IZ attenuation significantly decreased with MacTel severity, while overlap with IZ and EZ loss significantly increased. Overlap with IZ loss peaked in moderate MacTel (Stages 3–5). Longitudinal imaging showed that new EZ loss at 6 months was largely predicted by baseline IZ loss. Conclusions Worsening MacTel severity is characterized by greater overlap between DCP telangiectasia and zones of increasing severity of photoreceptor disruption, with EZ loss enlarging over time within areas of preexisting IZ disruption. We suggest that IZ disruption may indicate early photoreceptor dysfunction that eventually progresses to EZ loss, with IZ loss being a more reliable metric than IZ attenuation. Additional studies will be necessary to further explore long-term photoreceptor changes and evaluate their relationship with visual function in MacTel.

Retinal Lineage Therapeutic Specific Effect of Human Orbital and Abdominal Adipose-Derived Mesenchymal Stem Cells

Retinal degenerative diseases are one of the main causes of complete blindness in aged population. In this study, we compared the therapeutic potential for retinal degeneration of human mesenchymal stem cells derived from abdominal subcutaneous fat (ABASCs) or from orbital fat (OASCs) due to their accessibility and mutual embryonic origin with retinal tissue, respectively. OASCs were found to protect RPE cells from cell death and were demonstrated to increase early RPE precursor markers, while ABASCs showed a raise in retinal precursor marker expression. Subretinal transplantation of OASCs in a mouse model of retinal degeneration led to restoration of the RPE layer while transplantation of ABASCs resulted in a significant restoration of the photoreceptor layer. Taken together, we demonstrated a lineage-specific therapeutic effect for either OASCs or ABASCs in retinal regeneration.

The MicroRNA miR-18a Links Proliferation and Inflammation During Photoreceptor Regeneration in the Injured Zebrafish Retina

In mammals, photoreceptor loss causes permanent blindness, but in zebrafish (Danio rerio), photoreceptor loss reprograms Müller glia to function as stem cells, producing progenitors that fully regenerate photoreceptors. MicroRNAs (miRNAs) regulate neurogenesis in the CNS, but the roles of miRNAs in injury-induced neuronal regeneration are largely unknown. In the embryonic zebrafish retina, miRNA miR-18a regulates photoreceptor differentiation. The purpose of the current study was to determine in zebrafish the function of miR-18a during injury-induced photoreceptor regeneration. RT-qPCR, in-situ hybridization and immunohistochemistry showed that miR-18a expression increases throughout the retina by 1-day post-injury (dpi) and increases through 5 dpi. To test miR-18a function during photoreceptor regeneration, we used homozygous miR-18a mutants (miR-18ami5012), and knocked down miR-18a with morpholino oligonucleotides. During photoreceptor regeneration, miR-18ami5012 retinas have fewer mature photoreceptors than WT at 7 and 10 dpi, but there is no difference at 14 dpi, indicating that photoreceptor regeneration is delayed. Labeling dividing cells with bromodeoxyuridine (BrdU) showed that at 7 and 10 dpi, there are excess Müller glia-derived progenitors in both mutants and morphants, indicating that miR-18a negatively regulates injury-induced proliferation. Tracing BrdU-labeled cells showed that in miR-18ami5012 retinas excess progenitors migrate to other retinal layers in addition to the photoreceptor layer. Inflammation is critical for photoreceptor regeneration, and RT-qPCR showed that in miR-18ami5012 retinas, inflammatory gene expression and microglia activation are prolonged. Suppressing inflammation with dexamethasone rescues the miR-18ami5012 phenotype. Together, these data show that during photoreceptor regeneration in zebrafish, miR-18a regulates proliferation and photoreceptor regeneration by regulating the inflammatory response.

Sequential PBM–Saffron Treatment in an Animal Model of Retinal Degeneration

Background and Objectives: Saffron treatment and photobiomodulation (PBM) are non-invasive therapeutic approaches able to mitigate and stabilize retinal degenerative diseases such as age-related macular degeneration (AMD). Although different, these therapies partially match their modulated pattern of genes. Recent attempts to find an additive effect by coadministration of saffron and PBM have failed. Instead, in this study, a different protocol to increase neuroprotection by providing consecutive saffron and PBM treatment administration is suggested. Materials and Methods: Albino rats, whose retinal damage was caused by light exposure (LD, light damage), were subjected to differential treatment protocols before and after LD: (1) PBM followed by saffron; and (2) single treatments of PBM. Thinning of the photoreceptor layer and neuro-inflammatory markers for gliosis and microglia were assessed via immune-histochemical techniques. Results: Results confirm that PBM and saffron alone cope with retinal neurodegenerative processes, preserving retinal thickness and gliosis and microglia invasion in a differential way. However, the synergistic effect of the combined treatment was restricted to the early neuroinflammation, even when provided sequentially. Conclusion: The broad spectra of action of both neuroprotectants require further investigation to identify other key pathways helpful in enhancing the effects of these two approaches in combination.

ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model

Retinitis Pigmentosa (RP) is a blinding disease that arises from loss of rods and subsequently cones. The P23H rhodopsin knock-in (P23H-KI) mouse develops retinal degeneration that mirrors RP phenotype in patients carrying the orthologous variant. Previously, we found that the P23H rhodopsin protein was degraded in P23H-KI retinas, and the Unfolded Protein Response (UPR) promoted P23H rhodopsin degradation in heterologous cells in vitro. Here, we investigated the role of a UPR regulator gene, activating transcription factor 6 (Atf6), in rhodopsin protein homeostasis in heterozygous P23H rhodopsin (Rho+/P23H) mice. Significantly increased rhodopsin protein levels were found in Atf6−/−Rho+/P23H retinas compared to Atf6+/−Rho+/P23H retinas at early ages (~ P12), while rhodopsin mRNA levels were not different. The IRE1 pathway of the UPR was hyper-activated in young Atf6−/−Rho+/P23H retinas, and photoreceptor layer thickness was unchanged at this early age in Rho+/P23H mice lacking Atf6. By contrast, older Atf6−/−Rho+/P23H mice developed significantly increased retinal degeneration in comparison to Atf6+/−Rho+/P23H mice in all retinal layers, accompanied by reduced rhodopsin protein levels. Our findings demonstrate that Atf6 is required for efficient clearance of rhodopsin protein in rod photoreceptors expressing P23H rhodopsin, and that loss of Atf6 ultimately accelerates retinal degeneration in P23H-KI mice.

Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report

Background To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. Case presentation An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation. Conclusion Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.

Assessment of the clinical effectiveness of idiopathic macular ruptures surgical treatment of a large and medium diameter using modified inverted flap technology of internal limiting membrane (preliminary results)

Purpose. To assess the clinical effectiveness of surgical treatment of medium-and large-diameter idiopathic macular ruptures (IMR) using a modified technology by inversion and fixation of a free flap of the internal limiting membrane (ILM). Methods. A prospective study was conducted in 11 patients (11 eyes), 9 women and 2 men with medium-and large-diameter IMR. Mean age - 67.3 ± 5.38 (55-80) years. Patients with penetrating IMR of 2-4 stages according to the J. Gass classification. All patients underwent optical coherence tomography (OCT) along with traditional ophthalmological methods. The scans were performed in Retina Map, Cross line, Radial line, and Angio Retina modes. The obtained images were used to measure the parameters of the macular rupture (MR) of the retina manually. All patients underwent surgical treatment of IMR according to the proposed method. Results. In all cases, 1 day after the surgery, the closure of the gap was achieved according to ophthalmoscopy. 1 month after the surgery, according to OCT, 3 patients (27.2%) had a defect in the photoreceptor layer, 4 patients (36.3%) had deformity or peripheral non-attachment of the edges of the ILM flap, and 2 patients (18.1%) had a combination of these defects. According to OCT data in the Angio Retina mode, changes in the parameters of retinal blood flow were noted: there was a significant, moderate expansion of the avascular zone, accompanied by a moderate decrease in retinal perfusion. Despite this, there was a significant increase in visual acuity in the postoperative period. Conclusion. Endovitreal intervention for medium-and large-diameter macular ruptures using a modified technology by inversion and fixation of an ILM free flap is highly effective, as well as a low-traumatic treatment method that allows achieving anatomical closure of the macular defect and improving visual functions.

Analysis of the process of recovery of the foveolar region after surgery of idiopathic macular ruptures by the «temporal inverted VPM flap» method

Purpose. To analyze the recovery of the foveolar region after successful surgery of idiopathic macular rupture (IMR) using the "temporal inverted VPM flap" method. Material and methods. In 33 patients (34 eyes) aged 65.2±8.1 years, operated on for stage II-IV IMR according to J. Gass (1995), in the postoperative period for up to 1 year, changes in the foveolar region were studied by optical coherence tomography (OCT). Results. Recovery of the foveolar area began from the first days after the operation and lasted for 12 months. In the period from 1 week to 1 month, the recovery and approximation to the U-shaped foveolar contour was noted in all patients. At the final follow-up period: the outer boundary membrane and the ellipsoid zone were completely restored in 26/44 (76%) and 23/34 (68%) eyes, respectively; the average central retinal thickness decreased from 396±62.6 microns to 194±66 microns (p<0.05); the corrected distance visual acuity (CDVA) increased from 0.07±0.04 to 0.35±0.21 (p<0.05). Conclusion The "temporal inverted VPM flap" method is highly effective in the surgery of idiopathic macular ruptures. The process of restoring the microstructures of the foveolar zone begins from the first days after the IMR surgery using the "temporal inverted VPM flap" method, is gradual and lasts up to one year from the start of treatment. The main stages of restoration of the microstructures of the foveolar region are: mechanical overlap of the macular rupture with HPV flaps, filling of the IMR lumen with a "glial plug", restoration of the external photoreceptor layer of the fovea. Key words: foveolar region, outer layers of the retina, idiopathic macular rupture, temporal inverted VPM flap, optical coherence tomography.

Central Serous Chorioretinopathy: A Review of Pathogenesis, Risk Factors, Diagnostic Methods and the Current Treatments

Central serous chorioretinopathy (CSCR) is characterized by serous detachment of the neurosensory layer at the macula. It has a relatively high recurrence rate and mainly affecting middle-aged males. The etiology and pathogenesis of the disease still remain ambiguous. But choroidal changes which increase choroidal vascular permeability are the basic pathology of CSCR. Different diagnostic methods such as FAF, FFA, OCT, OCTA, ICG could be used to detect its biomarkers such as choroidal thickness, choroidal vascularity index, hyperreflective dots for exact diagnosis and treatment response. Acute CSCR generally self-limited, but in recurrent or chronic forms may cause permanent visual loss due to progressive and irreversible damage in the photoreceptor layer of retinal pigment epithelium atrophy. Several treatment alternatives have been reported, such as PDT, intravitreal Anti-VEGF, TTT, Laser, Mineralocorticoid receptor antagonist for chronic and recurrent CSCR.