Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution.

Human organoids recapitulating the cell-type diversity and function of their target organ are valuable for basic and translational research. We developed light-sensitive human retinal organoids with multiple nuclear and synaptic layers and functional synapses. We sequenced the RNA of 285,441 single cells from these organoids at seven developmental time points and from the periphery, fovea, pigment epithelium and choroid of light-responsive adult human retinas, and performed histochemistry. Cell types in organoids matured in vitro to a stable "developed" state at a rate similar to human retina development in vivo. Transcriptomes of organoid cell types converged toward the transcriptomes of adult peripheral retinal cell types. Expression of disease-associated genes was cell-type-specific in adult retina, and cell-type specificity was retained in organoids. We implicate unexpected cell types in diseases such as macular degeneration. This resource identifies cellular targets for studying disease mechanisms in organoids and for targeted repair in human retinas.

Real-World Clinical Results with the Hoya Vivinex Impress Intraocular Lens with Enhanced Depth of Focus.

BACKGROUND: In cataract surgery, intraocular lenses (IOLs) with enhanced depth of focus are an option to correct presbyopia. The purpose of this quality assurance analysis was to evaluate visual acuity and patient satisfaction after implantation of the Hoya Vivinex Impress IOL. METHODS: The Hoya Vivinex Impress IOL was implanted in patients undergoing cataract surgery at the Pallas Klinik, Olten, Switzerland. Five weeks postoperatively, a clinical examination and a survey on patient satisfaction were conducted. RESULTS: A total of 17 eyes (9 patients; mean age 64 years) underwent cataract surgery with implantation of a Hoya Vivinex Impress IOL. Five weeks postoperatively, mean uncorrected distance visual acuity (UDVA) was 0.2 logMAR, uncorrected intermediate visual acuity (UIVA) was 0.0 logMAR, and uncorrected near visual acuity (UNVA) was 0.2 logMAR. The mean distance-corrected visual acuity results were 0.0 logMAR, 0.1 logMAR, and 0.3 logMAR, respectively. Reading the newspaper without glasses was possible for 33.4% of patients. Visual disturbances such as halos and glares were not reported. CONCLUSION: Cataract surgery with Hoya Vivinex Impress IOL implantation revealed good distance and intermediate vision and, in some patients, functional near vision as well as a high patient satisfaction.

Immunohistochemical Findings in Retrocorneal Membranes of Eyes with Corneal Decompensation after Complicated Intraocular Surgery.

BACKGROUND: Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS: Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS: On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS: In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium.

674 Cases of Late Postoperative Intraocular Lens Opacification of a Hydrophilic-Hydrophobic Acryl Intraocular Lens in Switzerland and Retrospective Opacification Risk Factor Assessment of 212 Cases.

PURPOSE: To report the prevalence of late postoperative opacification of a hydrophilic and hydrophobic acrylic intraocular lens (IOL) and to assess the risk factors in a subset of 212 eyes of patients referred to the University Eye Department in Basel, Switzerland. DESIGN: Retrospective case series. METHODS: A survey was performed at all large ophthalmological clinics in Switzerland regarding exchanged Lentis LS-502-1 lenses, and the number of affected eyes was counted. Moreover, consecutive patients who were referred to a tertiary clinic between September 2015 and November 2016 with Lentis LS-502-1 opacification were investigated. Peri- and postoperative charts, medical history, and topical and systemic medications were assessed. RESULTS: A total of 674 opacified Lentis LS-502-1 lenses have been reported in Switzerland, and 212 consecutive eyes of 182 patients were included in the study. All IOLs had a similar pattern of opacification with a yellowish, diffuse appearance, and most of them showed a small, paracentral, roundish area that was less affected or not at all. Arterial hypertension (73%), hypercholesterolemia (34%), and diabetes (21%) were the main associated systemic diseases, and statins (34%) and betablockers (34%) were the main treatments used. CONCLUSIONS: The prevalence of IOL opacification was 9.9%. No associated systemic eye disease or medications could be detected, which was implicated in the opacification process. The reason for opacification remains unclear, but it seems to be unrelated to the patient's state; therefore, it is attributed to primary calcification.

Evaluation of Bicanalicular Nasolacrimal Duct Intubation as an Adjunct in Surgical Ectropion Correction.

Background and Objectives: We aimed to analyze and compare the outcomes of conventional ectropion surgery procedures with and without concurrent bicanalicular nasolacrimal duct intubation to identify if the combination of procedures could serve as a novel surgical approach to treat lower eyelid ectropion. Materials and Methods: A retrospective review of all patients who underwent surgical correction for lower eyelid ectropion at the Cantonal Hospital of Aarau between January 2019 and December 2020 was performed. Patient medical records were examined for etiology, surgical correction technique and intra- and postoperative complications. The postoperative punctal position, the pre- and postoperative epiphora and reoperation rate were also documented. Two study groups consisting of cases with isolated and combined procedures were compared, with respect to postoperative punctual and lower lid position. Results: A total of 53 lower eyelids (35 patients) were included in this study. Six months postoperatively, the correct punctum position (p = 0.1188) and improvement of epiphora (p = 0.7739) did not significantly differ between the two groups. More complications were seen in the nasolacrimal duct intubation group (p = 0.0041), which consisted of cheese wiring and one tube dislocation. Conclusion: In our study, bicanalicular nasolacrimal intubation during ectropion surgery does not seem to improve the outcome of ectropion surgery and is, therefore, not recommended on a routine basis.

Intraocular cataract lens replacement and light exposure potentially impact procedural learning in older adults.

Procedural learning declines with age and appropriately timed light exposure can improve cognitive performance in older individuals. Because cataract reduces light transmission and is associated with cognitive decline in older adults, we explored whether lens replacement (intraocular blue-blocking [BB] or UV-only blocking) in older patients with cataracts enhances the beneficial effects of light on procedural learning. Healthy older participants (n = 16) and older patients with post-cataract surgery (n = 13 with BB or UV lens replacement) underwent a randomized within-subject crossover laboratory design with three protocols. In each protocol, 3.5 hr dim-dark adaptation was followed by 2 hr evening blue-enriched (6,500K) or non-blue-enriched light exposure (3,000K or 2,500K), 30 min dim post-light, ~8 hr sleep and 2 hr morning dim light. Procedural learning was assessed by the alternating serial reaction time task (ASRT), as part of a larger test battery. Here, ASRT performance was indexed by type of trial (random or sequence) and sequence-specific (high or low probability) measures. During evening light exposure, we observed a significant effect of the interaction of "group" versus "light condition" on the type of trial (p = .04; p = .16; unadjusted and adjusted p-values, respectively) and sequence-specific learning (p = .04; p = .16; unadjusted and adjusted p-values, respectively), whereby patients with UV lens replacement performed better than patients with BB lens or non-cataract controls, during blue-enriched light exposure. Lens replacement in patients with cataracts may potentially be associated with beneficial effects of blue light on procedural learning. Thus, optimizing spectral lens transmission in patients with cataracts may help improve specific aspects of cognitive function, such as procedural learning.

[Prospective Cohort Study of In-Hospital Patients Undergoing Ophthalmic Surgery for the Validation of ClassIntra: Classification of Intraoperative Adverse Events]. / Prospektive Kohortenstudie bei stationären augenchirurgischen Patienten für die Validierung der ClassIntra-Klassifikation für unerwünschte intraoperative Ereignisse.

BACKGROUND: To the best of our knowledge, there is no validated classification to assess intraoperative adverse events (iAEs) in ophthalmic surgery. ClassIntra is a newly developed classification for surgery- and anaesthesia-related iAEs that has been recently validated in various surgical disciplines, but not in ophthalmic surgery. We aim to assess the validity and practicability of ClassIntra in patients undergoing ophthalmic surgery. METHODS: A consecutive sample of in-hospital patients undergoing any type of ophthalmic surgery was included in this single-centre prospective cohort study. iAEs were classified using ClassIntra, consisting of 5 severity grades according to the symptoms of the patient and the required treatment. All patients were followed for two weeks to record all postoperative adverse events according to Clavien-Dindo. The primary endpoint was the risk-adjusted association between the most severe iAE and the weighted sum of all postoperative adverse events within the two-week follow-up using the Comprehensive Complication Index (CCI). In addition, ophthalmologists and anaesthesiologists were asked to complete an online survey assessing the severity of iAEs for 10 fictitious clinical case scenarios. Reliability was assessed by comparing the clinicians' ratings to the prespecified benchmark rating of the study team. RESULTS: In this study, 100 in-hospital patients with an average age of 64 years (SD 15) were included. The majority of all patients were ASA II (n = 53, 53%) or III (n = 42, 42%). Thirty-two iAEs were recorded in 22 patients (17 grade I, 12 grade II, 3 grade III). Ninety-four postoperative adverse events occurred in 50 patients (44 grade I, 36 grade II, 14 grade IIIa). We found a mean difference in CCI of 2,1 (95% confidence interval [CI] - 2,5 to 6,8) per one unit increase in severity grades of ClassIntra. Fifty ophthalmologists and anaesthesiologists completed the online survey (response rate 54%). The intraclass correlation coefficient was 0,79 (95% CI 0,64 to 0,94). CONCLUSIONS: The application of ClassIntra during daily routine in ophthalmic surgery showed the usefulness and practicability of this classification for the standardised assessment of intraoperative adverse events. Although construct validity could not be demonstrated, the good reliability in the survey's rating underlines the criterion validity of this newly developed classification in ophthalmic surgery.

Comparison of an Er: YAG laser osteotome versus a conventional drill for the use in osteo- odonto-keratoprosthesis (OOKP).

OBJECTIVES: The osteo-odonto-kerato-prosthesis (OOKP) procedure is a complex, multi-stage, multidisciplinary surgical intervention for the treatment of severe corneal blindness. One step of the OOKP consists of creating a precise hole into a tooth in which an optic cylinder is subsequently inserted; its shape must ensure a perfect watertight fit. The Er: YAG laser (L) used in this study is part of CARLO®, the first laser osteotome that enables surgical planning based on computed tomography data, robot guidance, and a precise execution of laser cuts in teeth and bone tissue, using laser photoablation rather than conventional mechanical methods. The purpose of this study was to assess whether the Er: YAG laser is non-inferior compared to a conventional drill. METHODS: Thirty-two bovine incisors were grounded to a thickness of 1.5 mm. In 16 teeth, a 3.5 mm hole was drilled progressively into each tooth, using dental burs (B) of increasing diameter that were attached to a fixed drill machine. In the other 16 teeth, a hole was created using an Er: YAG laser at a wavelength of 2.94 µm (Part of CARLO®). In seven teeth of each group, the cylinder was inserted and fixated with polymethylmethacrylate (PMMA) bone cement. In the remaining seven teeth of each group, the cylinder was inserted without fixation material (press-fit). After bonding and drying, all specimens were stored in water until force measurements were recorded using a uniaxial traction machine. The force required to move the optical cylinder out of the hole in the tooth was measured using an Instron 3344 testing system. Scanning electron microscope (SEM) and light microscope (LM) visualization of the holes created with the laser and the drill were performed in two teeth (SEM)/four teeth (LM) per method. RESULTS: Significant differences (P < 0.001) were found for the following parameters: B PMMA versus B press-fit; B PMMA versus L press-fit; L PMMA versus B press-fit; L PMMA-L press-fit. This shows that PMMA bone cement fixation is superior to press-fit. No significant differences were found between B PMMA-L PMMA (P = 0.93) and B press-fit-L press-fit (P = 0.83). The SEM pictures showed a smoother surface using L. CONCLUSIONS: The laser cut holes were as strong as bur-drilled holes, although SEM pictures showed a smoother surface of the laser cut holes. Hence, laser osteotomes open the possibility to custom fit the hole exactly to the width of the cylinder, which represents a potential advantage of the laser over the conventional bur. Lasers Surg. Med. 51:531-537, 2019. © 2019 Wiley Periodicals, Inc.

[Clinical Outcomes after Keraring Implantation for Keratoconus Management in Thin Corneas]. / Klinische Ergebnisse nach Keraring-Implantation zur Behandlung von Keratokonuspatienten mit sehr dünnen Hornhäuten.

BACKGROUND: The aim of our study was to evaluate the clinical outcomes after Keraring implantation for keratoconus in patients with thin corneas. PATIENTS AND METHODS: Ten eyes from 10 patients with keratoconus, who underwent femtosecond laser-assisted Keraring implantation for keratoconus, were included in this retrospective study. Uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), keratometric readings, central corneal thickness and thinnest corneal pachymetry have been evaluated preoperatively and 6 months after the Keraring implantation. RESULTS: UCVA, BCVA and keratometric readings improved at 6 months postoperatively. CONCLUSIONS: Our data showed significant keratometric amelioration and visual improvement after Keraring implantation for keratoconus in patients with thin corneas at 6 months postoperatively.

Corneal Endothelial Decompensation after Ocular Chemical Burn: Description of a New Finding.

BACKGROUND: Ocular chemical burn is an ophthalmological emergency. Therefore, chemical injuries should be promptly addressed in order to initiate the appropriate treatment as soon as possible and optimize the visual prognosis. We present a retrospective study of ten cases with ocular chemical burn including one with superglue and one with a liquid plaster material injury and describe their clinical course. HISTORY AND SIGNS: Ten adult patients (34 - 92 years, 8 males) presented with moderate to severe alkali or neutral chemical burns in our emergency clinics. They exhibited a variable degree of conjunctival injection, limbal ischemia, corneal erosion, and Descemet's folds. THERAPY AND OUTCOME: Patients were treated and complete corneal epithelial closure was achieved in all cases without significant signs of limbal stem cell insufficiency. Corneal endothelial insufficiency was observed in all cases. Nine patients had to be listed for corneal endothelial keratoplasty and one was treated with Descemet's stripping endothelial automated keratoplasty. CONCLUSIONS: Isolated corneal endothelial decompensation after chemical burns has not yet been described. The pathophysiological explanation of this observation remains, however, unknown. In view of this rare complication, it is important to follow patients after chemical ocular burn for possible development of endothelial decompensation.

Evaluation of Visual Comfort and Mental Effort Under Different Light Conditions for Ultraviolet-Absorbing and Additional Blue-Filtering Intraocular Lenses for Cataract Surgery.

PATIENTS AND METHODS: Patients with an ultraviolet blocking lens (UV) (n = 5) or blue filter lens (BB) (n = 8) after intraocular lens (IOL) replacement for cataract and age-adjusted controls (AACs) (n = 16) underwent a balanced crossover within-subject design. After 1.5 h of dark adaptation, they were exposed to polychromatic light at 6500 K (blue-enriched) and 2500 K and 3000 K (non-blue-enriched) for 2 hours in the evening. Visual comfort and mental effort were repeatedly assessed by the Visual Analogue Scale (0 - 100) and the Visual Comfort and Mental Effort Rating Scale (0 - 100) for each light condition. The results were compared using mixed model analysis. RESULTS: The mean (± SD) age for AAC and patients with UV or BB was 69.8 ± 6.2 y, 70.8 ± 4 y, and 63.6 ± 5.6 y, respectively. Irrespective of the light condition, patients with UV and BB felt mentally more tired during the experiments compared to AACs (F = 6.15, p = 0.003). However, patients with BB were mentally more motivated to perform the exercises compared to patients with UV and AACs (F = 8.1, p < 0.001). Patients with BB perceived ambient light as less glary (F = 4.71, p = 0.01) than patients with UV. Blue ambient light was felt less intensely in patients with BB (F = 2.51, p = 0.042) compared to those with UV and the AACs. CONCLUSION: Lens replacement in older cataract patients may increase visual comfort and minimize mental effort. While subtle, the magnitude of these effects may depend on the type of intraocular lens. BB intraocular lenses may have potential benefits, as ambient light is perceived as having less glare and less visual tension.

[Capsulorhexis Real-Life - Experienced Surgeon versus Femto Laser Assisted Cataract Surgery (FLACS) as Reported in Literature]. / Kapsulorhexis Real-Life ­ erfahrener Operateur versus Literaturdaten zur Femto Laser Assisted Cataract Surgery (FLACS).

BACKGROUND: Capsulorhexis is one of the most important steps in cataract surgery. Good centration, circular overlap in sufficient size and a circular edge without tears result in good centration of the intraocular lens (IOL). In this study, the capsulorhexis results of an experienced surgeon are compared with reported data in femtolaser assisted cataract surgery (FLACS). PATIENTS AND METHODS: 105 consecutive operations were photographically documented; in 81 cases size and overlap were analysed retrospectively. The surgeon's personal anterior capsular tear rate was taken from the EUREQUO database. RESULTS: Average rhexis size was 5.03 ± 0.3 mm; the difference between the two measured diameters was 0.28 ± 0.18 mm. Circular overlap was found in 88.9% of cases. No radial tears were observed in 8000 operations in EUREQUO, resulting in a rate of less than 0.0125% in manual surgery. CONCLUSIONS: The overlap rate of manual surgery was comparable to FLACS; whether the slightly 'rounder' capsulotomy is clinically relevant remains unclear. The risk of an anterior capsular tear is very low in the hands of an experienced surgeon and even lower than with FLACS.

Cataract Surgery in High Hyperopia.

BACKGROUND: Although cataract surgery is a well-established and standardised procedure, it can be demanding and associated with higher complication rates in high hyperopia. We present clinical data for highly hyperopic patients who underwent cataract surgery over a 12-year period (2005 - 2016) and at a single centre. PATIENTS AND METHODS: Out of a total of 11 434 cataract operations, 41 highly hyperopic eyes (SN60AT ≥ 31 dpt) were included for analysis. We compared the target spherical equivalent to the final postoperative spherical equivalent for five different formulas. We also reviewed the best corrected distance visual acuity (BCDVA) before and after surgery and any complications. RESULTS: LogMAR BCDVA increased significantly from a mean of 0.5 before to 0.37 after surgery (p = 0.02). The main reasons for the reduced final BCDVA were glaucoma, Fuchs corneal endothelial dystrophy, and age-related macular degeneration. One eye suffered a radial capsule tear and received a sulcus implanted intraocular lens (IOL). There was no statistically significant difference between formulas with respect to aberration of the final spherical equivalent. CONCLUSIONS: Patients with high hyperopia often have ocular comorbidities. Such eyes may be surgically challenging, resulting in reduced benefits from cataract surgery compared to normal eyes.