The biophysical property of the limbal niche maintains stemness through YAP.

The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control cell behavior in vivo. To address this question, we focused on the corneal epithelial SC model in which the SC niche, known as the limbus, is spatially segregated from the differentiation compartment. We report that the unique biomechanical property of the limbus supports the nuclear localization and function of Yes-associated protein (YAP), a putative mediator of the mechanotransduction pathway. Perturbation of tissue stiffness or YAP activity affects SC function as well as tissue integrity under homeostasis and significantly inhibited the regeneration of the SC population following SC depletion. In vitro experiments revealed that substrates with the rigidity of the corneal differentiation compartment inhibit nuclear YAP localization and induce differentiation, a mechanism that is mediated by the TGFß-SMAD2/3 pathway. Taken together, these results indicate that SC sense biomechanical niche signals and that manipulation of mechano-sensory machinery or its downstream biochemical output may bear fruits in SC expansion for regenerative therapy.

Severely Elevated Intraocular Pressure Following Traumatic Asphyxia: A Case Report.

BACKGROUND: Traumatic asphyxia is a syndrome caused by a sudden pressure rise in the chest caused by crushing injury of the thorax or upper abdomen. It is associated with a variety of thoracic injuries, neurological symptoms, and ocular complications. CASE REPORT: We report an unusual case of traumatic asphyxia complicated by severe, sight-threatening, elevation in intraocular pressure. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: After initial stabilization, the treatment of patients with traumatic asphyxia is supportive and is mainly directed toward the accompanying injuries and complications. A complete and prompt ophthalmologic examination, including tonometry, should be an integral part of the secondary survey. This is particularly important in patients who cannot report visual impairment, such as children or unconscious patients.

Predicting Post-Cataract Surgery Visual Acuity in Vitrectomized Eyes: The Efficacy and Accuracy of "Lambda" Retinometry.

BACKGROUND AND OBJECTIVE: Determine the ability of Lambda retinometry to predict post-cataract surgery visual acuity in vitrectomized eyes. PATIENTS AND METHODS: Prospective study including 47 cataract surgery candidates with a history of pars plana vitrectomy (PPV). Lambda retinometry using a hand-held Lambda retinometer and best-corrected visual acuity (BCVA) were measured preoperatively, and BCVA was reassessed postoperatively. RESULTS: Lambda predictions strongly correlated with postoperative BCVA (logarithm of the minimum angle of resolution [logMAR]) (P < .001, r2 = 0.57), especially combined with preoperative BCVA (logMAR) (P < .001, r2 = 0.65). In 89% of cases, postoperative BCVA was equal to or higher than the prediction. Neither cataract grades nor indications for PPV were associated with the accuracy of Lambda predictions (P = .882 and P = .790, respectively). Underestimation of visual outcome was more common than overestimation. A Lambda prediction of ≥ 20/40 (Snellen) had a positive predictive value of 85.7% and a negative predictive value of 73.6% for the postoperative outcome. CONCLUSIONS: Lambda retinometry can reliably predict the postoperative BCVA in cataract patients who previously underwent PPV, with a tendency towards underestimation. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:535-542.].

Interface Drainage and Antimicrobial Irrigation Avoid Repeat Keratoplasty for Post-DSAEK Cold Interface Abscess.

PURPOSE: To describe a surgical technique for the diagnosis and treatment of post-Descemet stripping automated endothelial keratoplasty (DSAEK) infectious interface keratitis presenting as a cold abscess. METHODS: This study included 2 eyes of 2 patients that developed delayed-onset interface infections after DSAEK. Through an anterior keratotomy, diagnostic samples for microbial culture and histopathology examination were collected, and empiric antibiotic therapy was delivered directly to the site of the infection at the graft-host interface. RESULTS: In both cases, microbiological examinations confirmed a fungal etiology consistent with Candida. Resolution of infection was achieved, and no signs of posterior segment involvement or recurrence of infection were observed. Both corneas remained clear with final visual acuity of 20/25 and 20/32. No case required additional surgical intervention or repeat keratoplasty after more than 15 months of follow-up. CONCLUSIONS: Interface drainage with antimicrobial irrigation may be considered for the management of post-DSAEK interface infections presenting as a peripheral cold abscess. By avoiding intraocular seeding of infectious pathogens, the anterior approach can achieve clinical resolution of infection, maintain visual function, and preserve the DSAEK graft, thereby obviating the need for a therapeutic keratoplasty.

Pneumatic Dissection for Large-Diameter (9-mm) Deep Anterior Lamellar Keratoplasty in Eyes With Previous Anterior Lamellar Keratoplasty.

PURPOSE: To evaluate the surgical and 3-year clinical outcomes of modified big-bubble 9-mm deep anterior lamellar keratoplasty (DALK) in eyes with previous ALK (ALK). METHODS: In this interventional case series, 21 consecutive eyes with unsatisfactory vision after ALK (superficial ALK n = 9; laser-assisted ALK n = 7; and epikeratophakia n = 5) underwent large-diameter (9-mm) DALK. The surgery involved deep trephination based on the anterior segment optical coherence tomography pachymetry measurement at 9-mm diameter, pneumatic dissection from the base of the trephination and limited stromal clearance of the optical zone (6 mm). Main outcome measures were success rates of pneumatic dissection, best spectacle-corrected visual acuity, and complication rates. RESULTS: Pneumatic dissection with type 1 bubble formation succeeded in 19 (90%) eyes. In the 2 remaining cases, the 6-mm optical zone was cleared by manual dissection. Perforation occurred in one of the latter cases; no procedure was converted to penetrating keratoplasty. One month after complete suture removal, the preoperative mean best spectacle-corrected visual acuity (0.75 ± 0.23 logMAR) improved to 0.09 ± 0.10 logMAR (P < 0.001) and remained stable up to 3 years after surgery. At the final follow-up, refractive astigmatism was ≤4.5 and <6 D in 20 (95%) and 21 (100%) eyes, respectively. Stromal rejection was observed in 2 eyes (10%) and was treated successfully with steroids. CONCLUSIONS: Even in eyes with previous ALK, pneumatic dissection can be achieved through a modified DALK technique with a low risk of complications and excellent visual and refractive outcomes.

Ten-year outcomes of microkeratome-assisted lamellar keratoplasty for keratoconus.

BACKGROUND/AIMS: To report the 10-year outcomes of modified microkeratome-assisted lamellar keratoplasty (LK) for keratoconus. METHODS: In this single-centre interventional case series, 151 consecutive eyes with keratoconus underwent modified microkeratome-assisted LK. Eyes with scars extending beyond the posterior half of the corneal stroma and preoperative thinnest-point pachymetry value of less than 300 µm were excluded. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunological rejection, ectasia recurrence and graft failure rates. RESULTS: Baseline BSCVA (0.89±0.31 logarithm of the minimum angle of resolution (logMAR)) significantly improved to 0.10±0.12 logMAR at year 3 (p<0.001), and remained stable up to 10 years. At 10 years, 94% of eyes saw ≥20/40, 61% saw ≥20/25 and 24% saw ≥20/20 Snellen BSCVA. At final follow-up, RA exceeding 4.5 dioptres was observed in 5 cases (4%). Endothelial cell loss was 25±17% at 1 year with an annual decline of 2% over 10 years. The 10-year cumulative risk for immunological rejection and graft failure was 8.5%, and 2.4%, respectively. No case developed recurrent ectasia at 10 years. CONCLUSION: Modified microkeratome-assisted LK results in stable visual and refractive outcomes with low rates of immunological rejection and graft failure in the absence of recurrence of ectasia for at least 10 years.

Three-Year Outcomes of Tri-Folded Endothelium-In Descemet Membrane Endothelial Keratoplasty With Pull-Through Technique.

PURPOSE: To assess the 3-year outcomes of tri-folded endothelium-in Descemet membrane endothelial keratoplasty (DMEK) using bimanual pull-through delivery technique. DESIGN: Interventional case series. METHODS: In this single-center study, we included 153 consecutive eyes that underwent DMEK for various indications (Fuchs endothelial corneal dystrophy [FECD]: n = 111; bullous keratopathy [BK]: n = 24; and failed graft: n = 18). DMEK grafts were loaded into a disposable cartridge in a tri-folded, endothelium-in configuration and delivered using bimanual pull-through technique. Main outcome measures were graft preparation and unfolding times, best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), and graft survival. RESULTS: Mean graft preparation time was 5.9 ± 1.1 minutes; and mean graft unfolding time was 2.9 ± 0.9 minutes. Excluding eyes with comorbidities, logarithm of minimum angle of resolution BSCVA improved significantly from baseline preoperative values of 0.92 ± 0.58 to 0.02 ± 0.07 at 1 year (P < .001) and remained stable up to 3 years. Mean postoperative ECD decreased significantly (P < .001) from eye bank values to 1,818 ± 362, 1,675 ± 372, and 1,580 ± 423 cells/mm2 at 1, 2, and 3 years, respectively. No significant differences in ECD were observed between eyes with FECD and BK, but ECD was significantly lower in eyes with previous failed graft (P < .05). Three-year cumulative graft survival rate was significantly (P < .001) lower for eyes with previous failed graft (71%) than for FECD (97%) and BK (92%). CONCLUSIONS: Tri-folded endothelium-in DMEK requires minimal time for graft unfolding, which is the surgical step considered most challenging by corneal surgeons. Visual outcomes and complication rates are not adversely affected by the modification of the surgical technique.

Initial High-Dose Prophylaxis and Extended Taper for Mushroom Keratoplasty in Vascularized Herpetic Scars.

PURPOSE: To report the outcomes of initial high-dose and extended taper of antiviral and steroid prophylaxis for the treatment of eyes with high-risk vascularized herpetic corneal scars that underwent 2-piece mushroom keratoplasty (MK). DESIGN: Prospective interventional case series. METHODS: In this single-center study, 52 consecutive eyes with vascularized (≥2 quadrants) herpetic corneal scars underwent 2-piece microkeratome-assisted MK. Initial high-dose and extended taper of combined oral and topical antiviral and steroid prophylaxis was administered. Outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), endothelial cell density, immunologic rejection, herpetic recurrence, and graft failure rates. RESULTS: Excluding patients with vision-impairing comorbidities, baseline BSCVA (1.73 ± 0.67 logMAR) significantly improved annually during the first 2 years (P < .001, P = .016), reaching 0.17 ± 0.18 logMAR at year 2, and remaining stable up to 10 years (P = .662). At 2 years, 86% of eyes saw ≥20/40, 55% saw ≥20/25, and 18% saw ≥20/20 Snellen BSCVA. RA exceeded 4.5 diopters in 7% of cases after wound revision for high-degree astigmatism in 7 cases. Endothelial cell loss was 40.9% at 1 year with an annual decline of 3.1% over 10 years. The 10-year cumulative risk for immunologic rejection, herpetic recurrence, and graft failure was 9.7%, 7.8%, and 7.6%, respectively. CONCLUSIONS: Initial high dose and extended taper of antiviral and steroid prophylaxis for MK in high-risk, vascularized herpetic corneal scars achieves clinical outcomes that remain stable for up to 10 years after surgery with minimal risk of immunologic rejection, herpetic recurrence and graft failure.

Preoperative Anxiety Levels and Pain during Cataract Surgery.

Purpose: To evaluate the correlation between pain during cataract surgery and preoperative anxiety.Methods: This prospective observational masked study included 103 eyes of 103 consecutive patients who underwent routine clear corneal incision phacoemulsification surgery at the Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel. Patients were interviewed prior to surgery and 5 min following surgery by two separate independent interviewers. Anxiety level was measured by the Visual Analog Scale for Anxiety (VASA) and pain by the Visual Analog Scale (VAS). The main outcome measure was the maximum amount of pain endured during the procedure using VAS.Results: The mean participant age was 68.9 ± 8.9 years, and 46.6% were male. Severe anxiety (VASA ≥ 7) and pain (VAS ≥ 7) were documented in 18.5 and 17.5% of patients, respectively. There was a statistically significant positive correlation between VAS and VASA (r = 0.62, p < .001) as well as between VAS and duration of surgery (r = 0.20, p = .04). There was no association between VAS and all other investigated parameters in the univariate analysis. In backward regression analysis, VASA was the only parameter that was significantly associated with VAS (R2 = 36.61%, p < .001). Patients with severe anxiety were >10 times more likely to experience severe pain, and a VASA > 4 predicted severe pain with a sensitivity of 88.9% and a specificity of 69.4%.Conclusions: One-fifth of patients experienced severe anxiety and pain. Preoperative anxiety levels were the only significant predictor of pain. Reducing preoperative anxiety in cataract patients is warranted.

Precision pulse capsulotomy complicated by radial tear of the anterior capsule: a proposed mechanism.

Zepto precision pulsed capsulotomy is an emerging technology aimed at providing a safer and more reproducible anterior capsulorhexis, with potential advantages in challenging cases. Initial reports suggest high safety, and thus far to our knowledge, no complications have been reported. Herein we report an unexpected complication. After the pulse delivery phase on a routine cataract case, a radial tear of the anterior capsule was observed. Upon careful review of the surgery video, an air bubble was noted, at the precise clock hour of the radial tear, trapped between the device wire and capsule. This air bubble presumably prevented the transfer of rapid phase transition at this site, interfering with capsule cleavage, and resulting in incomplete capsulotomy. Based on this observation, if a trapped air bubble is observed after the vacuum phase, we recommend applying more vacuum or disengaging and reattaching, before proceeding to the pulse delivery stage.

Focusing the surgical microscope.

A well-focused operating microscope addresses several needs that are all secondary to the surgeon's need to see clearly at all times. These needs include: the assistant; the sharpness of the video and monitor; as well as field of view, asthenopia, and focusing issues related to zoom, accommodation, and presbyopia. We provide a practical approach to achieve optimal focus that we call the sloping paper calibration method.