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Targeting shared pathways in tauopathies and age-related macular degeneration: implications for novel therapies.

The intricate parallels in structure and function between the human retina and the central nervous system designate the retina as a prospective avenue for understanding brain-related processes. This review extensively explores the shared physiopathological mechanisms connecting age-related macular degeneration (AMD) and proteinopathies, with a specific focus on tauopathies. The pivotal involvement of oxidative stress and cellular senescence emerges as key drivers of pathogenesis in both conditions. Uncovering these shared elements not only has the potential to enhance our understanding of intricate neurodegenerative diseases but also sets the stage for pioneering therapeutic approaches in AMD.

Open-source, 3D printable IOL holder for detailed, smartphone-based anterior segment photography.

Smartphones are increasingly relevant resources in medical practice as they are ubiquitous and reasonably cheap. Among the advantages of using smartphones in medical practise, there is the possibility of obtaining reproducible photographic documentation of various conditions. This is particularly true in the ophthalmic field, where anterior segment color photography plays a significant role in the diagnosis and the management of ocular surface diseases. Here we propose an original design for an open-source smartphone accessory for taking and sharing high-definition photographs of the anterior segment. It can be easily reproduced via 3D printing, and it only needs to be integrated with an intraocular lens (IOL), widely available to the majority of ophthalmologists. Compared to other solutions described previously, it allows a precise and reproducible placement of the IOL on the smartphone camera, avoiding manual positioning that could result tricky and time-consuming. The IOL holder is cheap, scalable, portable and it can be quickly assembled and disassembled, without permanently modifying the smartphone camera.

Comparative Analysis of Tomographic Indicators Forecasting Decompensation in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To compare the performance of 3 commercially available tomographers (the Pentacam Scheimpflug camera, the swept-source optical coherence tomography Casia, and the blue light slit-scanning tomographer Precisio) in the identification of patterns associated with Fuchs endothelial corneal dystrophy (FECD) decompensation. METHODS: This was a clinic-based cross-sectional imaging study. Pachymetry maps and posterior surface elevation maps were acquired with the 3 devices from 61 eyes affected by FECD. The maps were graded according to the evidence of tomographic patterns predictive of FECD decompensation (loss of parallel isopachs, displacement of the thinnest point, and focal posterior depression) by 2 blind cornea specialists. RESULTS: The loss of parallel isopachs was significantly less frequently evident in Pentacam pachymetry maps [8%, 95% confidence interval (CI) (3%, 18%)] compared with both the Casia [31%, 95% CI (20%, 44%), P = 0.01] and Precisio devices [24%, 95% CI (15%, 37%), P = 0.05]. The displacement of the thinnest point was graded as most evident in a significantly higher proportion of Precisio pachymetry maps [43%, 95% CI (31%, 55%)] compared with both the Pentacam [13%, 95% CI (6%, 24%), P = 0.001] and Casia devices [21%, 95% CI (12%, 33%), P = 0.03]. There were no significant differences in the identification of focal posterior depression on posterior elevation maps across the 3 devices. CONCLUSIONS: Identification of patterns predictive of FECD prognosis on pachymetry and posterior elevation maps is possible with different devices. However, their evidence varies across tomographers, and the results from different devices are not interchangeable.

Double trouble in DMEK surgery: Learning experience and review of the literature.

PURPOSE: To report a challenging Descemet Membrane Endothelial Keratoplasty (DMEK) case, complicated by intraoperative aqueous misdirection and spontaneous anterior chamber fibrin reaction. METHODS: A 70-year-old female affected by corneal edema due to Fuchs endothelial dystrophy underwent a triple procedure (cataract extraction - IOL implantation - DMEK surgery) in her left eye. This report illustrates the management of the intraoperative complications of aqueous misdirection syndrome and anterior chamber fibrin reaction. RESULTS: Despite the optimal management of the posterior pressure and the thorough removal of the fibrinous reaction during the case, the DMEK graft was not completely unfolded and centred at the end of the surgical procedure. Nonetheless, the patient showed good long-term anatomical and functional recovery: at the last follow-up (2 years after surgery), central corneal thickness was 526 µm with a best corrected visual acuity of 20/25 and an endothelial cell density of 1112 cell/mm2. CONCLUSION: Early recognition and prompt management of intraoperative aqueous misdirection syndrome and anterior chamber fibrin reaction during DMEK surgery is essential to ensure good functional and anatomical outcomes.

Quality assurance in corneal transplants: Donor cornea assessment and oversight.

The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.

Combined or sequential DMEK in cases of cataract and Fuchs endothelial corneal dystrophy-A systematic review and meta-analysis.

To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed after phacoemulsification and intraocular lens (IOL) implantation (sequential DMEK) and DMEK combined with phacoemulsification and IOL implantation (combined DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and cataract. Systematic literature review and meta-analysis performed according to the PRISMA guidelines and registered in PROSPERO. Literature searches were conducted in Medline and Scopus. Comparative studies reporting sequential DMEK and combined DMEK in FECD patients were included. The main outcome measure of the study was the corrected distance visual acuity (CDVA) improvement. Secondary outcomes were postoperative endothelial cell density (ECD), rebubbling rate and primary graft failure rate. Bias risk was assessed and a quality appraisal of the body of evidence was completed using the Cochrane Robin-I tool. A total of 667 eyes (5 studies) were included in this review, 292 eyes (43.77%) underwent a combined DMEK, while 375 (56.22%) eyes underwent a sequential DMEK surgery. We found no evidence of a difference between the two groups (mean difference, 95% CI) regarding: (1) CDVA improvement (-0.06; -0.14, 0.03 LogMAR; 3 studies, I2 : 0%; p = 0.86); (2) postoperative ECD (-62; -190, 67 cells/mm2 ; 4 studies, I2 : 67%; p = 0.35); (3) rebubbling (risks ratio: 1.04; 0.59, 1.85; 4 studies, I2 : 48%; p = 0.89); and primary graft failure rate (risks ratio: 0.91; 0.32, 2.57; 3 studies, I2 : 0%; p = 0.86). Of all the 5 non-randomized studies, all (100%) were graded as low quality. The overall quality of the analysed studies was low. Randomized controlled trials are needed to confirm no difference or superiority of one approach in terms of CDVA, endothelial cell count and postoperative complication rate between the two arms.

Changes in macular pigment optical density after full-thickness macular hole closure using inverted flap technique.

Full-thickness macular hole (FTMH) is a debilitating retinal disorder, particularly in its advanced forms, necessitating surgical intervention for vision restoration. This case report details the successful closure of a large FTMH using the inverted flap technique, highlighting the essential role of multimodal imaging, and particularly macular pigment optical density (MPOD) assessment, in preoperative and postoperative evaluation. A 55-year-old patient presented with severe vision loss in one eye due to a large FTMH. Surgery was performed by an expert vitreoretinal surgeon, resulting in significant postoperative improvements in visual acuity and retinal architecture. Multimodal imaging, including MPOD assessment, played a pivotal role in preoperative evaluation and postoperative monitoring. The notable increase in MPOD following successful surgery suggests its potential role as a valuable adjunctive biomarker associated with a good visual prognosis following this type of macular hole surgical interventions.

Glaucoma as a Tauopathy-Is It the Missing Piece in the Glaucoma Puzzle?

Glaucoma is a chronic neurodegenerative disorder affecting the visual system which can result in vision loss and blindness. The pathogenetic mechanisms underlying glaucomatous optic neuropathy are ultimately enigmatic, prompting ongoing investigations into its potential shared pathogenesis with other neurodegenerative neurological disorders. Tauopathies represent a subclass of neurodegenerative diseases characterized by the abnormal deposition of tau protein within the brain and consequent microtubule destabilization. The extended spectrum of tauopathies includes conditions such as frontotemporal dementias, progressive supranuclear palsy, chronic traumatic encephalopathy, and Alzheimer's disease. Notably, recent decades have witnessed emerging documentation of tau inclusion among glaucoma patients, providing substantiation that this ocular disease may similarly manifest features of tauopathies. These studies found that: (i) aggregated tau inclusions are present in the somatodendritic compartment of RGCs in glaucoma patients; (ii) the etiology of the disease may affect tau splicing, phosphorylation, oligomerization, and subcellular localization; and (iii) short interfering RNA against tau, administered intraocularly, significantly decreased retinal tau accumulation and enhanced RGC somas and axon survival, demonstrating a crucial role for tau modifications in ocular hypertension-induced neuronal injury. Here, we examine the most recent evidence surrounding the interplay between tau protein dysregulation and glaucomatous neurodegeneration. We explore the novel perspective of glaucoma as a tau-associated disorder and open avenues for cross-disciplinary collaboration and new treatment strategies.

OCT-A in chronic central serous chorioretinopathy treated with oral eplerenone and half-fluence photodynamic therapy: A comparative study.

PURPOSE: To evaluate retinal and choriocapillary vessel density (VD) changes in patients with chronic central serous chorioretinopathy (CSC) treated with half-fluence verteporfin photodynamic therapy (vPDT) or eplerenone, using optical coherence tomography angiography (OCTA). METHODS: Patients affected by CSC and treated with vPDT and eplerenone were retrospectively studied. At baseline and 3 months after each treatment, all patients underwent a complete ophthalmological examination, including an evaluation of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain optical coherence tomography (SD-OCT) and OCTA. RESULTS: Forty-eight eyes of patients with CSC were analysed. Twenty-four eyes were placed in the vPDT group, and 24 eyes formed the eplerenone group. In both groups, OCTA showed a significant improvement in the VD of deep capillary plexus (DCP) and choriocapillaris (CC) after treatments with respect to baseline (p < 0.001), whereas the VD of superficial capillary plexus (SCP) did not show significant differences (p > 0.05). The PDT group demonstrated a statistically significant increase in the VD of DCP and CC with respect to the eplerenone group (DCP p = 0.012; CC p = 0.004). A statistically significant reduction with respect to baseline in subfoveal choroidal thickness (SFCT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) and in central foveal thickness (CFT) (p = 0.001 for vPDT group; p = 0.001 for eplerenone group) was also found. The SFCT was significantly thinnest in the PDT group with respect to the eplerenone group (p = 0.021). CONCLUSION: OCTA allowed us to study retinal and choriocapillary vascular changes in patients with CSC treated with vPDT and eplerenone.

An unusual association of macular retinoschisis with progressive familiar intrahepatic cholestasis: A multimodal imaging study.

PURPOSE: To evaluate a case of macular retinoschisis associated with a TJP2 mutation in a young woman affected by a Progressive Familiar Intrahepatic Cholestasis (PFIC) using multimodal imaging. METHODS: Observational case report. RESULTS: A 35-year-old woman, undergone a liver transplant for PFIC, was referred to Eye Clinic for complete ophthalmological examination and multimodal imaging. Fundus examination showed no significant alterations in both eyes while multicolor image revealed the presence of several cystes in macular region. The autofluorescence image highlighted small areas of iperautofluorescence in macular region. En-face image showed a "coral shape pattern" and structural optical coherence tomography (OCT) revealed foveal hyporeflective cystic spaces in outer and inner nuclear layers, areas of splitting within the nerve fiber layer (schisis areas) and an initial preretinal fibrosis. Lastly, OCT-angiography (OCT-A) demonstrated small perifoveal teleangectasias and slight reduction of the foveal avascular zone area. CONCLUSION: Multimodal imaging could help to highlight the presence of a rare retinal disorder associated with a gene related systemic disease.