Corneal Haziness Research Articles

Multimodal Imaging in Mucolipidosis Type IV: Siblings With Novel Genetic Variant.

Utilization of multimodal imaging techniques to diagnose cases of mucolipidosis type IV (ML-IV) and report a new genetic variant. This study is a case report. Case 1 involves a 4-year-old boy with corneal haziness and global developmental delay who showed an increased reflectivity of the corneal epithelium on anterior segment optical coherence tomography (AS-OCT). In addition, neurologic evaluation was suggestive of ML-IV. Further genetics evaluation confirmed ML-IV. Histology of the button revealed a thickened epithelial basement membrane. Case 2, the younger sibling, showed a milder corneal haze with similar changes on AS-OCT prompting us to further evaluate for ML-IV by genetics (positive MCOLN1 gene mutation). Both instances highlighted varied ML-IV presentations, but a persistent feature was hyperreflective epithelium. Our study emphasizes AS-OCT's role in screening ML-IV and advocates the role of genetic counseling of affected parents. We present 2 South-Asian siblings with ML-IV with a new genetic variant, emphasizing the utility of detailed ophthalmic and neurologic assessments using multimodal imaging.

The eye in forensic practice: In the dead.

Post-mortem examination of the eye provides valuable forensic information yet is often overlooked. This brief review focuses on determining the cause/manner of death and post-mortem interval. External eye findings like corneal haziness and tache noire, combined with post-mortem changes in the iris, lens, retina and vitreous humour, can help estimate time since death. Ocular biometrics (iris/retinal scans) may facilitate identification. Age-related ocular changes can provide insights. The eye offers clues into personality (corneal tattooing, trichotillomania) and cause of death (petechiae in strangulation, retinal haemorrhages in abusive head trauma). Ocular trauma and underlying eye disease may be evident. Toxicology of vitreous humour can detect drugs/poisons. As a window into systemic disease and age-related changes, the eye aids pathology interpretations and, accordingly, post-mortem examinations have value. Ocular findings should not be overlooked in forensic examinations as they provide distinct information in determining cause/manner of death and post-mortem interval.

Effects of different preparation protocols of blood serum eyedrops on corneal healing after alkali burn: Clinical evaluation and α-SMA expression

Background: In cases of alkali burn, blood serum eyedrops may supply protein and growth factors. A standard preparation protocol is necessary for consistency in epitheliotropic capacity. Objective: We aim to evaluate how post-alkali-burn administration of blood serum eyedrops from different preparation protocols results in different outcomes on rabbits. Methods: This randomized experimental study used three treatments: placebo, non-diluted serum, and 25% concentration serum. We analyzed the corneal haziness, neovascularization degree, histopathological examination of neovascularization scores, and alpha-smooth muscle actin (α-SMA) expression. Results: Twelve rabbits (24 eyes) were split evenly into three treatment groups. On day 14, the group receiving the 25% concentration serum had the least corneal haziness (p = 0.005). No adverse effect was observed on the treated eyes. Histopathologically, no significant difference in neovascularization scores and α-SMA expression was observed. Conclusions: Treatment using the 25% concentration serum resulted in less corneal haziness, smaller defect size, and greater healing rate. There was also no significant difference in histopathological outcomes among the three treatment groups.

A Case of Corneal Ulcer Caused by Stenotrophomonas maltophilia in a Healthy Patient

Purpose: To report a case of corneal ulcer caused by <i>Stenotrophomonas maltophilia</i> monomicrobial infection in an otherwise healthy patient, devoid of underlying medical conditions or predisposing factors.Case summary: A 48-year-old male patient, who was normally healthy without a history of systemic disease, eye trauma, and eye surgery, presented with acute left eye pain that had manifested one day prior. Ophthalmic examination revealed conjunctival injection, corneal edema, and localized corneal ulceration in the left eye. Suspecting infectious keratitis, diagnostic procedures including gram staining, bacterial and fungal cultures, and antibiotic susceptibility testing were promptly instituted. Bacterial culture identified <i>S. maltophilia</i>, prompting an eight-week course of topical gatifloxacin therapy. The subsequent clinical course exhibited improvement, with lingering corneal haziness and the restoration of visual acuity to 1.0.Conclusion: The case featuring the single detection of <i>S. maltophilia</i>, known to cause hospital-acquired opportunistic infections, emphasizes the importance of culture and antibiotic susceptibility testing in the treatment of keratitis. Remarkably, in a patient with a normal immune status and in the absence of factors predisposing to <i>S. maltophilia</i> infections, there were no discernible causative factors damaging the ocular surface environment.

Blast Eye Injury After Mobile Phone Battery Explosion: A Case Report

Introduction : Injuries from mobile phone blasts have been on the rise in recent years. Mobile phone blasts cause serious ocular morbidity. We report a rare case of blast eye injury after mobile phone battery explosion.
 Case Illustration : A 16 years old woman presented with burning sensation on both the eyes, following a smartphone battery blast. Immediately, after disconnecting the phone from the charger, the battery exploded and the phone blew apart. Her presenting visual acuity was 1/300 and 1.0 in right eye and left eye. Examination revealed broad corneal haziness on right eye, charred lashes, circumciliary congestion, and multiple soot particles embedded over the cornea, conjunctiva, and the lid margins. The eyes were washed with copious ringer lactate and the debris was carefully removed. Topical preservative free lubricants, broad-spectrum antibacterial agent, corticosteroid, and cycloplegic agent were prescribed along with systemic nonsteroidal anti-inflammatory drug. The healing of epithelial defects started on the next day and was complete by the 14th day.
 Discussion : We describe an ocular blast injury due to mobile phone explosion. The mechanism of injury from battery blast could be a combination of mechanical (battery pieces), thermal, and chemical injuries. The vision can be saved if the ocular surface burns are treated promptly and properly.
 Conclusion : Mobile blast injury is emerging as a new mode of ocular trauma. Knowing proper management is very important to achieve the best result.

Biotinidase deficiency: a novel phenotype from a tertiary care centre

Biotinidase deficiency (BD) (OMIM 609019) autosomal recessive inherited metabolic disorder where enzyme biotinidase, is defective and biotin is not recycled in body. One novel phenotype reported from our tertiary care centre, 3-month-old baby presented with bilateral corneal haziness, development delay and seizures. Evaluation showed metabolic acidosis, persistent lactate elevation and MRI showed acute infract. Metabolic evaluation showed profound BD, confirmed by molecular testing. Treatment and follow up with biotin showed clearing of corneal opacity, resolution of bleed and improvement in development and seizures. BD has got wide range of clinical manifestations- neurologic, dermatologic, ophthalmologic and immunological features. Acute infract and corneal opacity are not yet reported in OMIM literature and BD not considered in differential diagnosis of stroke in metabolic disorders. Being clinicians, it is our responsibility to add novel associations and clinical findings and thus broaden the phenotype.

Successful Treatment of Microsporidial Keratoconjunctivitis (MKC) With a Combination of Topical Voriconazole 1% and Gatifloxacin 0.5%: A Large Case Series of 29 Patients.

This study aims to report the successful treatment of microsporidial keratoconjunctivitis (MKC) with the combination of topical drops of voriconazole (1%) and gatifloxacin (0.5%) in all 29 patients. Demography, clinical profile, and previous treatment history were also analyzed. A retrospective, non-comparative case series of all Gram stain-proven MKC from September 2021 to October 2022 was included in this study. Patients were given antimicrobials such as topical drops of voriconazole 1%, gatifloxacin 0.5%, or a combination of both in 29 patients based on the treatment response. Topical steroids were added to 31 patients for corneal haziness. A total of 33 patients were found to be positive for microsporidiosis confirmed by Gram staining. Twenty-four (72.7%) were men and nine (27.3%) were women. The mean age was 34.45±12. The presenting symptoms were mainly redness in 30 patients (90.9%), followed by watering in 13 (39.4%), foreign body sensation in 10 (30.3%), etc. Among the 23 patients (69%), a history of risk factors was identified, with 17 patients (51.5%) specifically reporting dust exposure as a major cause. MKCs were successfully treated with antimicrobials such as voriconazole 1% in three patients, gatifloxacin 0.5% in one patient, and a combination of both in 29 patients. Topical steroids were added to 31 patients for corneal haziness. At the last follow-up, a visually insignificant nummular corneal scar was noted in six patients. No drop in vision was noted in any of these patients at the end of the follow-up. No cases progressed to stromal keratitis and no surgical intervention was required in any cases. We successfully treated all 29 cases with a combination of voriconazole and gatifloxacin without requiring any surgical intervention or encountering stromal complications. This successful treatment in all 29 cases offers valuable insights into the potential of this drug combination, possibly attributable to its additive action or broad-spectrum coverage across various species.

Lens-induced Glaucoma, a Collateral Damage during COVID-19 Pandemic

Cataract if left untreated, can lead to complications such as lens induced glaucoma and permanent visual loss. The COVID-19 outbreak resulted in movement control orders causing closure and reduction of non-COVID hospital services resulting delayed appointment dates. This study described the side effects of delayed patient appointments due to COVID-19 pandemic. A 70-year-old man presented with right eye (RE) pain and redness. There was gradual reduction in RE vision over the last year but treatment was delayed due to pandemic. In examination, visual acuity on his RE was hand movement and left eye (LE) was 6/12 (ph6/12) and near vision of N5. The right pupil was mid-dilated, reacting sluggishly with presence of relative afferent pupillary defect. Intraocular pressure (IOP) on the RE was 54 mmHg and LE was 16 mmHg. Circumciliary injection of right conjunctiva with central corneal haziness was seen. The anterior chamber was deep with the presence of 3+ cells with whitish lens material at the pupillary axis. A Morgagnian cataract with phacodonesis was present. A diagnosis of lens induced glaucoma was made. Immediate reduction of IOP included topical and systemic medication and pain relief were instituted. Intracapsular cataract extraction with anterior vitrectomy and surgical peripheral iridectomy was performed. This highlights the late presentation of a patient with mature cataract during the COVID-19 pandemic. Patient awareness and education are essential in recognising the complications of mature cataract if it is presented later. A reminder of signs and symptoms of lens induced glaucoma should be conveyed to patient when appointment is delayed.

The Effect of Amniotic Membrane Extracted Eye Drop on Repairing The Corneal Epithelial in Patients after Trans-Epithelial Photorefractive Keratectomy: An Interventional and Historical Study.

Recent studies imply extensive applications for the human amniotic membrane (hAM) and its extract in medicine and ophthalmology. The content of hAM meets many requirements in eye surgeries, such as refractive surgery as the most important and commonly used method for treating the dramatically increasing refractive errors. However, they are associated with complications such as corneal haziness and corneal ulcer. This study was designed to evaluate the impact of amniotic membrane extracted eye drop (AMEED) on Trans-PRK surgery complications. This randomized controlled trial was performed during two years (July 1, 2019-September 1, 2020). Thirty-two patients (64 eyes), including 17 females and 15 males, aged 20 to 50 years (mean age of 29.59 ± 6.51) with spherical equivalent between -5 to -1.5 underwent Trans Epithelial Photorefractive Keratectomy (Trans-PRK) surgery. One eye was selected per case (case group) and the other eye was considered as control. Randomization was done using the random allocation rule. The case group was treated with AMEED, and the artificial tear drop every 4 hours. The control eyes received artificial tear drops instilled every 4 hours. The evaluation continued for three days after the Trans-PRK surgery. A significant decrease in CED size was found in the AMEED group on the second day after surgery (P=0.046). Also, this group had a substantial reduction in pain, hyperemia, and haziness. This study showed that AMEED drop can increase the healing rate of corneal epithelial lesions after Trans- PRK surgery and reduce the early and late complications of Trans-PRK surgery. Researchers and Ophthalmologists should consider AMEED as a selection in patients with persistent corneal epithelial defects and patients who have difficulty in corneal epithelial healing. We understood AMEED has a different effect on the cornea after surgery; therefore, the researcher must know AMEED's exact ingredients and help expand AMEED uses (registration number: TCTR20230306001).

Resolvin D1 Inhibits Corneal Inflammation in Staphylococcus Aureus Keratitis

ABSTRACT Purpose To investigate the role of lipid mediator, resolvin D1 (RvD1), in corneal inflammation. Methods The anti-inflammatory effect of RvD1 on stimulated human corneal epithelial cells (HCECs) was assessed. C57BL/6 mice corneas were abraded and treated with RvD1 after stimulation with Staphylococcus aureus. Cytokine levels in the corneas, cervical drainage lymph nodes (DLNs), and spleens were measured. Anterior segment photography and optical coherence tomography quantified the changes in corneal thickness and haziness. Neutrophil infiltration in the cornea was examined by haematoxylin and eosin (H&E) staining and immunohistochemistry. Results RvD1 significantly inhibited cytokine production in HCECs and mouse corneas, cervical DLNs, and spleens while stimulating interleukin-10 (IL-10) production. Corneal opacity development, thickening, and neutrophil infiltration significantly reduced in response to RvD1 stimulation in the S. aureus-infected mice corneas. Conclusion RvD1 inhibited S. aureus-induced corneal inflammation. These results potentiate RvD1 as an anti-inflammatory therapy for patients with corneal inflammation induced by bacterial keratitis.

One-year follow-up of patients with hyperopia undergoing photorefractive keratectomy with Allegretto WaveLight Eye Q 400.

This study aimed to examine the effectiveness of photorefractive keratectomy (PRK) in treating patients with cycloplegic hyperopia from +1.00 to +7.00 diopter using Allegretto wave Eye Q 400. This study was conducted on 25 patients with cycloplegic astigmatism ≤1 diopter and cycloplegic hyperopia between +1.00 and +7.00 diopters in 47 eyes, who successively entered into the study within 6 months and underwent PRK. Prior to PRK surgery, all the patients were examined for cycloplegic refraction (astigmatism and hyperopia), slit lamp, keratometry, fundus, and best-corrected (BCVA) and uncorrected visual acuity (UCVA) testing. These examinations were repeated after 1 week, 1 month, 3 months, 6 months, and 1 year postoperatively. The mean preop UCVA of patients was 0.76±0.28 (ranging from 0.00 to 1.3), which reached 0.19±0.22 (ranging from 0.00 to 0.78) one year after the surgery (P=0.000). There was a significant correlation between increasing astigmatism and preop cycloplegic hyperopia >5 diopters (P=0.000), corneal ring haziness at 12th months (P=0.000), and 12 months cycloplegic residual hyperopia ≥2.00 diopters (P=0.000). 53.2% of the eyes (with a mean grade of 2.34) were detected with corneal ring haziness at 12th months, which was significantly correlated with 12 months residual cycloplegic hyperopia of ≥2.00 diopters (P: 0.000) and cycloplegic sphere above 5 diopters (P=0.006). Although the use of photorefractive keratectomy (PRK) with Allegretto Eye Q 400 is associated with a decrease in the mean cycloplegic and improved UCVA and BCVA, its use is not recommended in cases with preop cycloplegic hyperopia above 5 diopters due to the high rate of induction of astigmatism, corneal haziness, and regression of hyperopia.

Blast Eye Injury After Mobile Phone Battery Explosion: How to Manage it?

Introduction: Injuries from mobile phone blasts have been on the rise in recent years. Lithium-ion batteries are the most common type found in cellphones and devices. In 2016 around 100 of the 2.5 million phone cell units have been recorded to have exploded. Mobile battery burst is a significantly underappreciated cause of serious ocular morbidity and could be a combination of mechanical, thermal, and chemical effects. Knowing proper management is very important to achieve the best result. Case presentation: We describe an ocular blast injury due to mobile phone battery explosion when plugged in to charge that experienced spasm and burned cilia, limbal ischemia, broad corneal haziness on both eyes, and visual acuity decreased. The fluorescein test was positive. We did proper irrigation and debris extraction around the ocular surface and periorbital tissue. It was treated with quinolone antibiotics eyedrop, atropine sulfate eyedrop, prednisolone eyedrop, and NSAID orally. In four days, the patient’s eye showed good clinical improvement with decreased corneal haziness with minimal epithelial defect. The visual acuity was improved on both eyes. Conclusions: Lithium-ion batteries are used in almost all smartphones and electronics. Lithium explosions can result in chemical and thermal burns on the ocular surface. Ocular alkali chemical injury combined with thermal and mechanical is an emergency case. The vision can be saved if the ocular surface burns are treated promptly and properly. These cases are required to raise public awareness about the potential risks of smartphone use, adopt safe practices as recommendations from the manufacturers, and avoid counterfeit products and such accidents.

A Rare Case of Bilateral Post Intravitreal Avastin Endophthalmitis with Bilateral Good Visual Outcome – A Case Report

This is a case report of post intravitreal injection endophthalmitis encountered at the University Teaching Hospitals–Eye Hospital in Lusaka, Zambia. Endophthalmitis is a clinical diagnosis made when intraocular inflammation involving both the anterior and posterior chambers is attributable to bacterial or fungal infection. Post injection endophthalmitis is a dreaded complication that occurs following intraocular surgery or procedures such as intravitreal administration of anti-vascular endothelial growth factors or corticosteroids. We attended to a rare case of bilateral post intravitreal injection endophthalmitis in a 51- year- old female patient who presented with bilateral severe pain and acute visual loss in both eyes following intravitreal injection of Avastin (bevacizumab) the previous day. On examination, there was severely decreased visual acuity from 6/36 right eye and 6/60 left eye to hand movement in both eyes. There was also corneal haziness, fibrin in the anterior chambers, hypopyon and vitreous cells in both eyes. A clinical diagnosis of bilateral post-injection endophthalmitis was made. There was immediate administration of intravitreal antibiotics of Vancomycin 1.0mg/0.1mL and Ceftazidime 2.25mg/0.1mL with intravitreal Dexamethasone 0.4mg/0.1ml stat dose and systemic ciprofloxacin 750mg 12 hourly for 7 days. Due to prompt diagnosis and treatment vision recovery was excellent in both eyes and both eyes were preserved.

Cataract surgery outcomes: comparison of the extracapsular cataract extraction and manual small incision cataract surgery techniques.

Blindness and visual impairment are public health problems and constitute an important socio-economic burden in sub-Saharan Africa. Understanding the outcomes of cataract surgery will improve our knowledge of risk factors for poor outcomes. Previous studies have focused exclusively on the phacoemulsification technique with limited attention to the extracapsular cataract extraction (ECCE) and manual small incision cataract surgery (MSICS) techniques. To compare the cataract surgery outcomes between the ECCE and MSICS techniques. The study was an observational research design that used the LogMAR visual acuity (VA) chart, subjective refraction, slit lamp and ophthalmoscope to collect data. The participants were followed for a period of six-weeks post-surgery and outcomes were recorded. Data were presented using frequencies, percentages and means ± standard deviation. The sample included 101 participants, with a mean age of 66.32 ± 15.99 years. Fifty and 51 participants had undergone the ECCE and MSICS techniques respectively. Overall, one-hundred participants had poor pre-surgery VA and subjective refractions were generally not possible due to the severity of cataracts present. The mean aided post-surgery VA was 0.31 LogMAR and 0.13 LogMAR in the ECCE and MSICS groups respectively (p < 0.001). The mean post-surgery refractive astigmatism was similar in the ECCE (-2.06 D) and MSICS (-1.80 D) groups (p = 0.110). The spherical equivalence was approximately -0.50 D higher in the MSICS group, but not statistically significant (p = 0.330). Approximately one out of every five participants (n = 21) had post-surgery ocular complications such as corneal opacity and haziness as well as posterior capsular absence. The MSICS technique showed better post-surgery outcomes than the ECCE technique.

Multi modal imaging in corneal edema after corneal collagen cross-linking (CXL); a case-based literature review

BackgroundKeratoconus (KCN) is a common ectatic disorder of the cornea. Corneal collagen cross-linking (CXL) is used as an effective option to slowdown the disease progression. Although CXL is considered a safe procedure, corneal endothelial damage, especially in corneal thickness of less than 400 μm, has been reported.Case presentationA 25-year-old man known case of KCN was referred with complaints about blurred vision and discomfort of the right eye 3 days after performing CXL. The preoperative thinnest point was 461 μm. His presenting BCVA was CF at 1 m. Examination showed central corneal edema and stromal haziness. ASOCT demonstrated increased central corneal thickness and very deep CXL line. In the confocal scan, anterior stroma showed hyper-reflective lines without recognizable cells and nerves, the middle stroma showed rare active and edematous keratocytes and a hyper-reflective reticular pattern with elongated keratocytes and needle-like structures involving the posterior stroma indicated increased depth of CXL. To manage the patient, debridement of loosened epithelium was done. Non-preservative steroid 1% eye drop was prescribed frequently. The corneal edema was completely resolved during 2 months with no need for surgical procedure and BCVA of 20/30 in his right eye.ConclusionThe corneal thickness of more than 400 μm cannot guarantee the absence of corneal edema after corneal collagen cross-linking, which can pertain to several factors such as inadvertently using of higher energy as well as the incorrect observance of all guidelines, instructions, and other precautions, even by a trained surgeon.

Topical Tacrolimus as an adjunct to Conventional Therapy for Stromal Herpetic Keratitis: a Randomized Clinical Trial.

PurposeThis study investigates the effects of 0.05% topical tacrolimus as an adjunct therapy for patients with non-necrotizing herpetic stromal keratitis (HSK).MethodsPatients with non-necrotizing HSK, referred to the Cornea Clinic at Hospital in Rasht, Iran, between September 2016 and February 2018, were randomly assigned to two groups. The case group (N = 25) and the control group (N = 25) received conventional treatment with systemic acyclovir and topical prednisolone. The case group (N = 25) additionally received 0.05% tacrolimus eye drops four times a day for one month. Complete ocular examinations, including best-corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) measurement, slit lamp biomicroscopy, and photo slit lamp imaging, were performed before treatment, and 3, 7, 14, 21, and 28 days after the intervention.ResultsThe mean age of the patients was 46.2 12.9 years, and 70% of the patients were male. There was no difference between the groups in terms of age, sex, and baseline ocular measurements (P 0.05). The case group had a lower mean logarithm of the minimum angle of resolution (LogMAR) for BCVA, lower grading scores, and steeper decreasing trends for corneal haziness, edema, neovascularization, and epitheliopathy compared to the control group after the second week (P 0.05), while IOP remained unchanged between groups (P 0.05).ConclusionThe addition of 0.05% topical tacrolimus enhances visual acuity and reduces corneal inflammation, neovascularization, and scarring; thus, it can used as an appropriate adjunct treatment for patients with HSK.

The healing effect of the collagen-glycosaminoglycan copolymer on corneal thinning

BackgroundTo study the healing processes of partial thickness wounds in the adult rabbit cornea after grafting a porous collagen-glycosaminoglycan copolymer matrix (CG).MethodsIn this study, the regeneration of surgically-induced rabbit corneal defect implanted with CG was investigated. The corneal partial thickness wound was created by 7.5 mm trephine. The wound was implanted with CG. Effects on wound healing was analyzed using clinical data on epithelial migration and corneal thickness, and histological data on collagen and alpha smooth muscle actin distribution.ResultsCompared with control group, CG induced a relatively severe inflammatory reaction in grafted cornea until the CG matrix was completely degraded. The new vessel ingrowth and stromal regeneration maintained the corneal thickness. The grafted cornea was significantly thicker (P < 0.001) than the control group. On day 90, the corneal opacity score of the control group was one and the grafted cornea was two.ConclusionCG copolymer matrix can successfully repair the damaged corneal stroma by injury, and regain its thickness. However, CG matrix induced inflammatory healing process thus causing mild corneal haziness and neovascularization.

Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy

BackgroundCorneal endothelial cell (CEC) disorders, such as Fuchs’s endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density.MethodsWe performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 μl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 μm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection.ResultsAt 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 μm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98).ConclusionsInjection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534.)

Feasibility of cell-based therapy combined with descemetorhexis for treating Fuchs endothelial corneal dystrophy in rabbit model.

Corneal transparency is maintained by the corneal endothelium through its pump and barrier function. Severe corneal endothelial damage results in dysregulation of water flow and eventually causes corneal haziness and deterioration of visual function. In 2013, we initiated clinical research of cell-based therapy for treating corneal decompensation. In that study, we removed an 8-mm diameter section of damaged corneal endothelium without removing Descemet’s membrane (the basement membrane of the corneal endothelium) and then injected cultured human corneal endothelial cells (CECs) into the anterior chamber. However, Descemet’s membrane exhibits clinically abnormal structural features [i.e., multiple collagenous excrescences (guttae) and thickening] in patients with Fuchs endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely affects the quality of vision, even in patients without corneal edema. The turnover time of cornea guttae is also not certain. Therefore, we used a rabbit model to evaluate the feasibility of Descemet’s membrane removal in the optical zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC injection. We showed that the corneal endothelium is regenerated both on the corneal stroma (the area of Descemet’s membrane removal) and on the intact peripheral Descemet’s membrane, based on the expression of function-related markers and the restoration of corneal transparency. Recovery of the corneal transparency and central corneal thickness was delayed in areas of Descemet’s membrane removal, but the cell density of the regenerated corneal endothelium and the thickness of the central corneal did not differ between the areas with and without residual Descemet’s membrane at 14 days after CEC injection. Here, we demonstrate that removal of a pathological Descemet’s membrane by a small descemetorhexis is a feasible procedure for use in combination with cell-based therapy. The current strategy might be beneficial for improving visual quality after CEC injection as a treatment for FECD.

Activation of TGF-\u03b2 signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive bilateral disease of corneal endothelium in which accumulation of extracellular matrix (ECM) and loss of corneal endothelial cells (CECs) are phenotypic features. The corneal endothelium maintains corneal transparency by regulating water hydration; consequently, corneal endothelial dysfunction causes serious vision loss. The only therapy for corneal haziness due to corneal endothelial diseases, including FECD, is corneal transplantation using donor corneas, and no pharmaceutical treatment is available. We provide evidence that the expression levels of transforming growth factor-β (TGF-β) isoforms and TGF-β receptors are high in the corneal endothelium of patients with FECD. A cell model based on patients with FECD shows that TGF-β signaling induced a chronic overload of ECM proteins to the endoplasmic reticulum (ER), thereby enhancing the formation of unfolded protein and triggering the intrinsic apoptotic pathway through the unfolded protein response (UPR). We propose that inhibition of TGF-β signaling may represent a novel therapeutic target that suppresses cell loss as well as the accumulation of ECM in FECD.