Comprehensive combined analysis of physician-initiated phase II and III clinical trials on a cultured human corneal endothelial cell product for treating bullous keratopathy.

To evaluate the efficacy and safety of a cultured human corneal endothelial cell (cHCEC) product in eyes with bullous keratopathy (BK). Combined analysis of multicenter phase II and III clinical trials. This analysis involved 15 BK eyes in the phase II trial and 12 BK eyes in the phase III trial that underwent cHCEC transplant therapy. Safety was assessed in all the cases. Efficacy was assessed in 17 cases with exclusion of the low- and medium-dose groups in the phase II trial. The primary endpoint was a corneal endothelial cell density of 1000 cells/mm2 or more at 24 weeks post-transplant, which was attained in 94.1% of the eyes (16 of 17), with a 95% CI of 71.3-99.9%. Additionally, 82.4% of the eyes (14 of 17) met the secondary endpoint of reduction in corneal thickness to less than 630 µm without corneal epithelial edema within the same time frame, with a 95% CI of 56.6-96.2%. The mean decrease in corneal thickness from baseline to 24 weeks post-transplant was -187.4 µm (95% CI, -240.2 µm to -134.5 µm). Furthermore, all the eyes exhibited improvement in best-corrected visual acuity from baseline to 24 weeks post-transplant (95% CI, 80.5-100.0%). By 24 weeks post-transplant, 88.9% of the patients (24 of 27) had experienced adverse events, which were mostly local, mild, and transient. The cHCEC product of this study reconstitutes the corneal endothelial layer with high cellular density and restores corneal thickness and improves visual acuity.

Busin Glide-Assisted Pull-Through Insertion of Artificial Corneal Endothelium (EndoArt).

Background: Currently, the push-in technique through the corneal tunnel using a blunt-tip spatula is used to insert an artificial corneal endothelium (EndoArt) into the anterior chamber (AC). The device is useful for patients with bullous keratopathy; however, it may be difficult to manipulate the very thin implant through hazy cornea. Unlike DMEK graft, it cannot be stained and the F-mark is faint. So, visualizing and orienting the implant is a real challenge especially through a hazy cornea and inadequate AC visualization. Therefore, alternative EndoArt implantation techniques are needed in patients with advanced endothelial dysfunction to avoid complications. Purpose: To report an alternative technique for EndoArt implantation using a Busin glide. Technique: The EndoArt was loaded onto the Busin glide with the concave side of the EndoArt facing upward and was then pulled/pushed into the Busin glide opening. After the Descemet's membrane and endothelium were detached and removed in a circular fashion in a patient with advanced corneal endothelial decompensation, the Busin glide was inserted into the corneal incision, and the EndoArt was slowly pulled into the AC using retractor forceps. Finally, the air was injected into the AC. Conclusion: The Busin glide-assisted pull-through technique smoothly and securely inserted the EndoArt into the AC without upside-down attachment. This alternative technique can be useful for patients with a history of repeat intraocular surgeries or trauma with severe corneal edema to avoid potential complications such as epithelial implantation cysts or downgrowth.

Efficacy of hypertonic saline in treatment of corneal edema: A randomized crossover trial.

Background: To determine the efficacy of sodium chloride (NaCl) 5% drops in comparison to 6% ointment and study tear Osmolarity as an objective measure correlating with clinical findings in the treatment of corneal edema. Methods: This is a prospective, randomized, interventional, open-label, crossover study of 40 eyes of 40 patients with corneal edema due to Bullous keratopathy and Fuchs endothelial dystrophy. Subjects were divided into 2 groups by simple randomization: group A received NaCl 5% drops and group B received NaCl 6% ointment. Both treatments were administered four times daily for seven days. Subsequently, after a 1-week wash-out period, switch over of treatment was done. Central corneal thickness (CCT) and tear osmolarity were primarily efficacy variables. Results: Baseline parameters were comparable. The median reduction in CCT from baseline (706.7 ± 58.41 µm), at 6 hours with NaCl 5% drops was 23 µm (-27, 74) and that with NaCl6% ointment was 37.5 µm (-7, 85). The reduction in CCT was more with 6% ointment (p = 0.013). The difference in reduction in CCT between two treatments at one week was not statistically significant, although there was a substantial reduction in thickness with each treatment individually. The change in tear osmolarity from the baseline at 2 Hours with both NaCl5% drops and 6% ointment was significant, and it remained so till 6 h. Side-effects such as stickiness, stinginess, blurring, and foreign body sensation were more with 6% eye ointment. Conclusion: Topical NaCl 6% eye ointment in QID dosage is more effective than NaCl 5% drops in the medical management of corneal edema. In patients symptomatically intolerant to ointment, NaCl 5% eye drops may be prescribed as an effective option.

Outcomes of retropupillary iris claw lens implantation in patients with intraocular lens dislocation and low (less than 1000 cells/mm2) corneal endothelial cell density.

BACKGROUND: Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm2) ECD. METHODS: We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm2 and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery. RESULTS: Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57-76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07-89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01). CONCLUSIONS: R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings.

Human corneal endothelial cell transplantation with nanocomposite gel sheet preserves corneal stability in post-corneal transplant bullous keratopathy: a 16-year follow-up.

Post-corneal transplantation endothelial decompensation and subsequent bullous keratopathy often result in unfavorable clinical outcomes regardless of the treatment strategy employed. In this report, we present the outcomes of a patient managed with in vitro expanded human corneal endothelial cell (HCEC) transplantation facilitated by a nanocomposite gel (NC gel) sheet over 16 years. A 40-year-old male patient who presented with signs of graft failure after penetrating keratoplasty underwent HCEC transplantation. Additionally, HCECs were obtained from a deceased donor, cultured in vitro, and transplanted onto an NC gel sheet as a temporary scaffold to support the transplanted cells until engraftment. At the 16-year follow-up, the cornea had remained stable and did not exhibit active disease manifestations. Notably, no new bullae were formed, and the epithelial surface appeared smooth without signs of active fluid transport abnormalities. Although a slight reduction in corneal thickness was observed, the disease-free region at the time of the intervention remained transparent. HCEC transplantation with NC gel sheets is a promising, minimally invasive approach for achieving long-term corneal stability in cases of bullous keratopathy following corneal graft failure. Importantly, this technique circumvents the need for complex procedures and utilizes corneal endothelial precursors derived from donor corneas discarded for lack of sufficient endothelial cells. After in vitro culture, these cells were successfully transplanted in three patients, proving that one donated eye can be useful in treating three eyes of three patients. This technique addresses the donor cornea shortage concerns and makes our concept "an-eye-for-eyes", a reality.

Absence of the Klotho Function Causes Cornea Degeneration with Specific Features Resembling Fuchs Endothelial Corneal Dystrophy and Bullous Keratopathy.

The Klotho loss-of-function mutation is known to cause accelerated senescence in many organs, but its effects on the cornea have not been published. The present study aims to investigate the effects of the Klotho null mutation on cornea degeneration and to characterize the pathological features. Mouse corneas of Klotho homozygous, heterozygous, and wild-type mice at 8 weeks of age for both genders were subject to pathological and immunohistological examinations. The results show an irregular topography on the corneal surface with a Klotho null mutation. Histological examinations revealed a reduced corneal epithelial cell density, endothelial cell-shedding, and decreased cornea stromal layer thickness in the absence of the Klotho function. Furthermore, guttae formation and the desquamation of wing cells were significantly increased, which was comparable to the characteristics of Fuchs endothelial corneal dystrophy and bullous keratopathy. The mechanism analysis showed multi-fold abnormalities, including oxidative stress-induced cornea epithelium apoptosis and inflammation, extracellular matrix remodeling in the stroma, and a disruption of epithelial repair, presumably through the epithelial-mesenchymal transition. In conclusion, cornea degeneration was observed in the Klotho loss-of-function mutant mice. These pathological features support the use of Klotho mutant mice for investigating age-related cornea anomalies, including Fuchs endothelial corneal dystrophy, bullous keratopathy, and dry eye diseases.

Novel technique to improves graft unfolding in vitrectomized eyes during Descemet membrane endothelial keratoplasty.

INTRODUCTION: Descemet membrane endothelial keratoplasty (DMEK) is commonly used to treat endothelial pathologies in bicameral pseudophakic eyes with a normal depth of the anterior chamber. However, performing this procedure on eyes that have undergone vitrectomy carries a higher risk of complications. Therefore, this report presents a novel technique for improving the unfolding of a DMEK graft in a vitrectomized eye. PRESENTATION OF CASE: A 49-year-old man with a history of complicated cataract surgery one year prior was referred to our clinic with pseudophakic bullous keratopathy in his left eye. The surgery involved a posterior capsular rupture, anterior vitrectomy, and implantation of a sulcus three-piece intraocular lens. DMEK and anterior vitrectomy were performed. However, the conventional tap technique was unsuccessful in unfolding the DMEK graft, owing to intraoperative hypotony and an inability to flatten the anterior chamber. DISCUSSION: To minimize excessive manipulation of the donor tissue, a 27-gauge cannula attached to a 3-cc syringe was used. A cannula was introduced through paracentesis near the edge of an unfolded DMEK graft. We then created a suction force by pulling back the plunger while slowly moving the needle backward during the graft unfolding. The postoperative course was uneventful, with a clear and fully attached DMEK graft. CONCLUSIONS: This technique reduces the complexity of DMEK graft unfolding in vitrectomized eyes, enabling easier and more controlled unfolding. However, further research with larger patient populations is required to determine the clinical relevance of this method.

Restoring the Ocular Integrity of Perforated Corneal Ulcer Using Living Surgical Donor Tissues Derived From Keratoplasty in the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) caused an unprecedented crisis for corneal surgeons who were forced to strategize for an acute shortage of tissues. Here, we report the initial clinical outcomes of utilizing host corneal buttons derived from optical penetrating keratoplasties of pseudophakic bullous keratoplasty (PBK) patients. Two patients presented to our department with a perforated fungal corneal ulcer in one eye during the COVID-19 pandemic. One eye of each of the patients was operated on with non-vascularized host cut tissues preserved in glycerin. The tissues were secured using 10-0 nylon sutures. Good anatomical integrity was achieved in both eyes. An optical penetrating keratoplasty (PK) was done in both eyes after one year for visual rehabilitation, with a final visual acuity of 20/120 and 20/80, respectively, at six months. In conclusion, therapeutic PK using host tissues obtained from the recipients of optical PK is a safe and effective option to restore ocular integrity during a shortage of fresh or glycerol-preserved corneas. However, optical PK is required for the final visual rehabilitation.

Optical coherence tomographic features of feline acute corneal hydrops: A case report.

OBJECTIVE: The objective of the study was to describe the optical coherence tomographic features of a cat with acute corneal hydrops. ANIMAL STUDIED: A 4-year-old castrated male domestic shorthaired showing conjunctival redness, ocular discharge, and intermittent squinting of both eyes with asymmetrical disease onset. METHODS: Complete ophthalmic examination and optical coherence tomography were performed. RESULTS: On slit-lamp biomicroscopic examination, severe intrastromal fluid pockets with profound bullae were observed in the dorsomedial region in both eyes. A diagnosis of feline acute corneal hydrops was made in both eyes. Optical coherence tomography revealed profound stromal lamellar separation representing heterogeneous reflective areas, and fluid pockets and bullae of variable size were concomitant to Descemet's membrane detachment demonstrated by a well-defined homogeneous hyporeflective area. Upon reevaluation 30 days during healing process for both eyes, the thickened epithelia and the thinning pan-stromal areas were identified as homogeneously hyper-reflective epithelia and as heterogeneous hyper-reflectivity, respectively. A thickened posterior corneal surface was shown as heterogeneous with patchy hyper-reflectivity. Additionally, Descemet's membrane detachment in the initial presentation had two distinct forms suspicious of Descemet's membrane rupture in each eye: a break with rolled ends and a break with flat ends. CONCLUSION: To the author's knowledge, this study represents the first documentation of in vivo detection of Descemet's membrane detachment and presumed rupture in a cat experiencing acute corneal hydrops. These observations strongly indicate that Descemet's membrane detachment/rupture acts as a most likely risk factor in the onset of acute corneal hydrops in cats.

Statistical analysis plan for the phaco TIp position during clear corneal Phacoemulsification Surgery (TIPS) randomized controlled trial.

BACKGROUND: Cornea is the most important refractive media in the eye, and damage to the corneal endothelium is one of the most common causes of poor visual outcome following cataract surgery, particularly in those with predisposing factors. The role of phaco tip position during phacoemulsification on corneal endothelial damage is ambiguous, and there is no consensus regarding the most cornea-friendly phaco tip position (bevel-up or bevel-down). The objective of the trial is to compare the effect of phaco tip position (bevel-up vs. bevel-down) during phacoemulsification using direct chop technique on corneal endothelial cell count. METHODS AND DESIGN: TIPS is a randomised, multicentre, parallel-group, triple-masked (participant, outcome assessor, and statistician) trial with 1:1 allocation ratio. A total of 480 eligible participants, aged > 18 years with immature cataract, will be randomly allocated into bevel-up and bevel-down groups at two centres. Randomisation will be stratified according to the cataract grade. The primary outcome is postoperative endothelial cell count at 1 month. Secondary outcomes are central corneal thickness on postoperative days 1, 15, and 30 and difference in intraoperative complications. CONCLUSION: In this paper, we describe the detailed statistical analysis plan (SAP) for the TIPS trial, which was prepared prior to database lock. The SAP includes details of planned analyses and unpopulated tables, which will be reported in the publications. We plan to lock the database in July 2023 and publish the results later in the same year. SAP Version 0.1 (dated: 28 April 2023) Protocol version:2.0 TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2019/02/017464. Registered on 5 February 2019; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=29764&EncHid=&userName=2019/02/017464.

Evaluation of biophysical alterations in the epithelial and endothelial layer of patients with Bullous Keratopathy.

The cornea is a fundamental ocular tissue for the sense of sight. Thanks to it, the refraction of two-thirds of light manages to participate in the visual process and protect against mechanical damage. Because it is transparent, avascular, and innervated, the cornea comprises five main layers: Epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. Each layer plays a key role in the functionality and maintenance of ocular tissue, providing unique ultrastructural and biomechanical properties. Bullous Keratopathy (BK) is an endothelial dysfunction that leads to corneal edema, loss of visual acuity, epithelial blisters, and severe pain, among other symptoms. The corneal layers are subject to changes in their biophysical properties promoted by Keratopathy. In this context, the Atomic Force Microscopy (AFM) technique in air was used to investigate the anterior epithelial surface and the posterior endothelial surface, healthy and with BK, using a triangular silicone tip with a nominal spring constant of 0.4 N/m. Six human corneas (n = 6) samples were used for each analyzed group. Roughness data, calculated by third-order polynomial adjustment, adhesion, and Young's modulus, were obtained to serve as a comparison and identification of morphological and biomechanical changes possibly associated with the pathology, such as craters and in the epithelial layer and exposure of a fibrotic layer due to loss of the endothelial cell wall. Endothelial cell membrane area and volume data were calculated, obtaining a relevant comparison between the control and patient. Such results may provide new data on the physical properties of the ocular tissue to understand the physiology of the cornea when it has pathology.

Outcomes and success of amniotic membrane transplantation for the treatment of corneal diseases.

PURPOSE: The amniotic membrane (AM), the inner layer of the placenta, is a semitransparent, avascular, and thin tissue that is useful due to its structure. Amniotic membrane transplantation (AMT) avoids the need for keratoplasty to prevent corneal perforating. The purpose of the study was to evaluate the visual (gain of or no change in visual acuity) and corneal outcomes (closure of the ulcer or corneal healing) of AMT in patients with ocular surface diseases. MATERIALS AND METHODS: This was a retrospective case control study (success or failure of the surgery). It was undertaken at a single academic center. The study cohort consisted of subjects with ocular surface diseases. Patients were treated with AMT for refractory ocular surface diseases. They were divided into five subgroups according to the preoperative diagnosis. The technique of AMT used was the onlay method with two layers of AM. Primary outcome measures included best corrected visual acuity (BCVA), the number of AMTs, and reepithelization of the corneal epithelium at the end of the treatment. Two weeks to six months were given to consider epithelial closure. Treatment success was defined as corneal healing within 6 months. RESULTS: A total of the 66 eyes of 66 patients (39 male/27 female) with a mean age of 44 ± 23 years (range 1-88 years) were included in the study. A single AMT procedure achieved epithelial closure in 74.2% (n = 49) of the eyes (53% in <15 days, 19.6% in 15-30 days, and 1.5% in 1-6 months). The fastest reepithelization occurred in neurotrophic keratopathy, 76.9% of which cases occurred within 15 days after the AMT procedure. Treatment failure was observed in five patients (7.5%), four with keratitis and one with neurotrophic keratopathy. The highest closure rates were found in persistent epithelial defects, graft-versus-host disease (GvHD), and bullous keratopathy, although there was no statistically significant difference in BCVA. Pairwise comparisons were made of neurotropic keratoplasty versus bullous keratopathy (P = 0.025), neurotrophic keratopathy versus keratitis (P = 0.004), GVHD versus keratitis (P = 0.003), and lastly, GvHD versus bullous keratopathy (P = 0.023). CONCLUSIONS: AMT is a safe, valuable, and fast treatment technique to treat corneal epithelial defects stemming from different etiologies that are refractory to conventional treatment.

Identification and Analysis of Primary Cilia in the Corneal Endothelial Cells of Patients with Bullous Keratopathy.

PURPOSE: To identify primary cilia in human corneal endothelial cells (CECs) obtained from patients with bullous keratopathy (BK). METHODS: This study involved CEC specimens obtained from 10 eyes of 10 consecutive patients (three males and seven females; mean age: 74.5 years, range: 68-90 years) with BK who underwent Descemet's stripping automated endothelial keratoplasty at Baptist Eye Institute, Kyoto, Japan between August 2019 and September 2020. Three corneal buttons obtained from 3 patients who underwent penetrating keratoplasty for keratoconus were used as 'non-BK' controls. All specimens were evaluated with immunofluorescence staining using an antibody against acetylated α-tubulin. RESULTS: Ciliary expression was observed in six of the 10 CEC specimens; i.e. in two specimens obtained from BK patients after glaucoma surgery (trabeculectomy), in two specimens obtained from patients with Fuchs endothelial corneal dystrophy, and in two specimens obtained from a patient with BK after laser iridotomy for primary angle closure. There was acetylated α-tubulin staining but no hair-like structures in two specimens, and ciliary expression was unknown in two specimens due to the absence of cells. The length of the primary cilia varied between all specimens. In contrast, no primary cilia were observed in the corneal buttons obtained from the three keratoconus patients. CONCLUSION: The findings in this study clearly demonstrate the expression of primary cilia in the CECs of patients afflicted with BK.

Anterior chamber intraocular lens removal combined with triple DMEK: Quadruple DMEK for bullous keratopathy.

PURPOSE: To present the outcomes of a patient with anterior chamber intraocular lens (ACIOL) related endothelial decompensation who underwent Descemet membrane endothelial keratoplasty (DMEK) and cataract surgery with intraocular lens (IOL) implantation in the capsular bag (so-called triple DMEK) combined with ACIOL removal (quadruple DMEK) in both eyes. METHODS: Case report. RESULTS: A 58-year-old female patient was referred due to decreased visual acuity within the last 18 months. She had a history of iris-claw ACIOL implantation 17 years before. The corrected distance visual acuity (CDVA) was 20/40 in both eyes. Due to low endothelial cell density and increased corneal thickness, ACIOL removal combined with triple DMEK (as quadruple DMEK) was performed for both eyes. Despite a graft detachment that was successfully managed with re-bubbling in the first eye, both eyes showed an increase in the CDVA (20/25 and 20/32, respectively) without any other significant complications in the follow-up of the patient. The corneas of both eyes were clear postoperatively. CONCLUSION: This case report demonstrated that quadruple DMEK may provide feasible management for chronic endothelial cell decompensation secondary to iris-claw ACIOL implantation.

[Corneal changes in Fuchs endothelial corneal dystrophy and bullous keratopathy]. / Izmeneniya rogovitsy pri endotelial'noi distrofii Fuksa i vtorichnoi bulleznoi keratopatii.

OBJECTIVE: Evaluation of structural and immunohistochemical features of cornea in Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). MATERIAL AND METHODS: Group 1 - 44 patients (46 eyes) with FECD, group 2 - 42 patients (42 eyes) with BK. All patients underwent keratoplasty. Preoperative anterior segment optical coherence tomography (AS-OCT, RTVue-100, Optovue, USA) was performed. Endothelium-Descemet membrane (EDM) complexes, corneal buttons were obtained intraoperatively. Morphological (H&E staining) and immunohistochemical (primary antibodies to pancytokeratin, vimentin, fibronectin) studies were performed at the light microscope level (Leica DM-2500, Leica Application Suite V4.8, Leica Microsystems, Switzerland). RESULTS: A direct correlation is found between the results of DM analysis in vivo with OCT and ex vivo with light microscopy. DM thickness (AS-OCT) was significantly greater in FECD (23.0 [19.0; 27.0] µm), than in BK (13.0 [12.0; 14.0] µm). Morphological study of EDM and corneal buttons showed similar difference in DM thickness: 17.9 [16.1; 20.0] µm in FECD and 11.9 [11.3; 13.0] µm in BK. Irregular optical density of stroma is a feature of edema and local fibrosis. In FECD and BK pancytokeratin is expressed in epithelial and endothelial cells, vimentin - in keratocytes, macrophages and vascular endothelium, fibronectin - in DM. In FECD, vimentin is expressed in endothelial cells. CONCLUSION: FECD and BK are associated with different DM' and endothelium' abnormalities, which lead to similar changes of stroma and epithelium. AS-OCT is a useful method of FECD and BK in vivo diagnostics and the selection of treatment option.

Descemet Membrane Endothelial Keratoplasty with cornea press technique and implantation of a Carlevale scleral-fixated intraocular lens.

Purpose: We describe a combined Descemet Membrane Endothelial Keratoplasty (DMEK) using the Cornea-press (C-Press) technique, with implantation of a new sutureless, scleral fixated intraocular lens (IOL) (Carlevale, Soleko), in a case of bullous keratopathy and IOL mispositioning. Observations: Two scleral pockets were created along two scleral radial incisions, 180° apart, followed by two 23 G sclerotomies at the pockets' sites. After removal of the dislocated IOL through a corneoscleral incision, posterior vitrectomy was completed. The Carlevale IOL was injected into the anterior chamber (AC) and placed above the iris. The haptics were then externalized using opening distal forceps through the sclerotomies, and the plugs were secured in the scleral pockets. DMEK was then performed using the "C-press" technique, where corneal indentation allowed to artificially shallow the AC to ensure successful graft unrolling. Fifteen months postoperatively, the cornea was clear, the Carlevale IOL well positioned, and the patient's vision improved. Conclusions and importance: DMEK using the C-Press technique, combined with a sutureless, scleral-fixated IOL such as the Carlevale in a single procedure, may be a safe and effective option to restore vision in case of bullous keratopathy and dislocated IOL.

Endothelial dysfunction of the cornea after exposure to sprayed venom from hornets.

PURPOSE: Ocular injuries due to Hymenoptera venom are uncommon and most injuries occur on the ocular surface. We reported two rare cases of corneal endothelial damage caused by hornet venom that was sprayed, not injected, through stinging in the eye. OBSERVATIONS: Case 1: A 57-year-old male patient was injured when a hornet sprayed venom into his left eye. He was referred to our hospital because the edoema and epithelial erosion of the cornea persisted. The patient presented with bullous keratopathy, asymmetrical iris atrophy, irreversible mydriasis, and glaucoma. His cataract progressed, and his best-corrected visual acuity was 0.03. Cataract surgery was performed after anti-inflammatory treatment with steroids, and Descemet-stripping automated endothelial keratoplasty was performed 6 months later. The patient recovered well postoperatively: his best-corrected visual acuity improved to 1.0 and he continued his glaucoma treatment. Case 2: A 75-year-old male patient had damage to his corneal epithelium, severe conjunctivitis, and conjunctival edoema when sprayed hornet venom entered his left eye. At initial presentation, the corneal endothelial cell density had decreased to 1042 cells/mm2. The conjunctival sac was washed, and steroid and topical antibacterial instillations were administered. His best-corrected visual acuity improved from 0.07 at the initial visit to 0.5. However, the corneal opacification and glaucoma persisted, and 3 months later the corneal endothelial cell density decreased to 846 cells/mm2. CONCLUSIONS AND IMPORTANCE: Corneal injuries caused by sprayed hornet venom are rare; however, they can cause intense anterior chamber inflammation and severe, irreversible corneal endothelial damage. In such cases, prompt initial treatment, the administration of adequate anti-inflammatory medication, and careful evaluation of the corneal endothelium are required.

Role of corneal collagen cross-linking in bullous keratopathy: A systematic review.

Corneal cross-linking (CXL), a corneal strengthening procedure, is known to alter anterior stroma swelling behavior and is one of the treatment modalities of bullous keratopathy (BK). There are multiple studies published on the role of CXL in the treatment of BK. These articles had heterogeneous study population, different protocols used, and variable conclusions. This systematic review aimed to determine the role of CXL in the treatment of BK. The primary outcomes considered were changes in central corneal thickness (CCT) after 1, 3, and 6 months of CXL. The secondary outcome measures were changes in visual acuity, corneal clarity, subjective symptoms, and complications after CXL. We included randomized control trials (RCTs), observational and interventional studies, and case series with reports of more than 10 cases in this review. In RCTs, the mean pre-CXL CCT (794.0 ± 178.5 µm) in the intervention group (n = 37), decreased at 1 month (750.9 ± 154.3 µm) followed by a subsequent increase, but this difference was not significant during the 6-month follow-up (P- value 0.28, 0.82, and 0.82 at 1, 3, and 6 months, respectively). In noncomparative clinical studies (n = 188), the mean pre-CXL CCT (794.0 ± 178.5 µm) decreased at 1 month (710.9 ± 127.2 µm, P < 0.0001). Seven of the 11 articles included in the review reported no significant improvement in vision with CXL. The initial improvement in corneal clarity and clinical symptoms was not sustained. Current evidence suggests that CXL has short-term efficacy in the treatment of BK. More RCTs with high-quality evidence are needed.

Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy.

(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy. (2) Methods: Cell injections of corneal endothelial cells were performed in 45 eyes in a rabbit model of BK. AS-OCT imaging and central corneal thickness (CCT) measurement were performed at baseline and on day 1, day 4, day 7 and day 14 following cell injection. A logistic regression was modelled to predict successful corneal deturgescence and its failure with cell aggregate visibility and CCT. Receiver-operating characteristic (ROC) curves were plotted, and areas under the curve (AUC) calculated for each time point in these models. (3) Results: Cellular aggregates were identified on days 1, 4, 7 and 14 in 86.7%, 39.5%, 20.0% and 4.4% of eyes, respectively. The positive predictive value of cellular aggregate visibility for successful corneal deturgescence was 71.8%, 64.7%, 66.7% and 100.0% at each time point, respectively. Using logistic regression modelling, the visibility of cellular aggregates on day 1 appeared to increase the likelihood of successful corneal deturgescence, but this did not reach statistical significance. An increase in pachymetry, however, resulted in a small but statistically significant decreased likelihood of success, with an odds ratio of 0.996 for days 1 (95% CI 0.993-1.000), 2 (95% CI 0.993-0.999) and 14 (95% CI 0.994-0.998) and an odds ratio of 0.994 (95% CI 0.991-0.998) for day 7. The ROC curves were plotted, and the AUC values were 0.72 (95% CI 0.55-0.89), 0.80 (95% CI 0. 62-0.98), 0.86 (95% CI 0.71-1.00) and 0.90 (95% CI 0.80-0.99) for days 1, 4, 7 and 14, respectively. (4) Conclusions: Logistic regression modelling of cell aggregate visibility and CCT was predictive of successful corneal endothelial cell injection therapy.

Bilateral malignant glaucoma with bullous keratopathy: A case report.

BACKGROUND: Malignant glaucoma, caused by aqueous misdirection, is a challenging post-surgical complication presented with normal/high intraocular pressure and shallowing of the central and peripheral anterior chambers. Its incidence is about 0.6%-4.0%. It can be secondary to filtering surgeries, laser iridotomy, and cataract surgery. Short axial length and a history of angle closure glaucoma are its main risk factors. Here, we report a bilateral malignant glaucoma with bullous keratopathy in the patient's left eye. CASE SUMMARY: We present a case of bilateral malignant glaucoma. The cause of malignant glaucoma for each eye of this patient was different. Hence, the management strategy and selection of surgical methods were also different. However, the normal anterior chamber was ultimately maintained, and maximum visual function was preserved. Even though the left eye received multiple surgeries and corneal endothelial decompensation occurred, the formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium. CONCLUSION: The formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium.