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Purpose: Scar contracture of the eyelid following facial burns often has adverse consequences. Total cicatricial contracture often makes adjustment flap translation challenging to implement. Previously used upper and lower eyelid adhesion methods are ineffective for patients with severe cicatricial contracture, and ectropion can easily recur. This study aimed to retrospectively examine upper and lower eyelid adhesions using an orbicularis oculi muscle flap and verify its stability., Methods: In patients with ectropion caused by severe scar contracture following head and face burns, we employed a tunnel orbicularis oculi muscle flap technique, which involved creating a tunnel between the skin and the tarsal plate of the eyelid, mobilizing the orbicularis oculi muscle, and rotating it into this tunnel to provide stable adhesion of the upper and lower eyelids. Full-thickness skin grafting was then performed. The eyelids were examined postoperatively to determine whether reoperation was necessary and to monitor for any potential complications., Results: This study included 26 patients and 46 eyes. No accidental disconnection occurred after eyelid adhesion, which lasted for an average of 21.87 ± 10.08 months before the eyelid adhesion was cut open. No complications or adverse reactions occurred, and the adhesions did not break unexpectedly., Conclusions: Repairing eyelid ectropion with the tunnel orbicularis oculi muscle flap is a simple procedure that immediately creates tension against upper and lower eyelid contractures, providing long-term stable adhesion. This method avoids structural disorders, such as eyelid margin scarring, minimally influences surrounding tissues, and has few postoperative complications. It holds great value for repairing eyelid tissue defects and warrants further study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Chemical burns of the ocular surface (CBOS) are emergencies of highest urgency. Therefore, an adequate emergency care is mandatory. Following a precise analysis of the initial damage, a staged therapeutic approach is used to prevent persistent impairment of the ocular surface. In the acute stage, the prevention of complications is targeted (symblepharon, conjunctival scarring, lacrimal stenosis, corneal ulceration, intraocular inflammation, elevated intraocular pressure, etc.). In later stages, if complications have developed, a secondary restoration of the ocular surface is focussed. Sometimes this requires several surgical interventions. Based on a review of international literature, this review highlights the pathophysiology according to different chemical agents, CBOS stages as well as main therapy strategies in early and advanced stages of CBOS. Acute treatment aims to lower inflammation, oxidative stress and tries to promote reepithelialisation. Besides conjunctival scarring, loss of goblet cells and corneal opacification a limbal stem cell insufficiency is the most harming complication. Several new techniques have been developed to recover the ocular surface with a sufficient and clear epithelial layer in order to avoid neovascularization of the cornea. The knowledge concerning the high risk potential for persistent visual impairment in CBOS patients and the ability for appropriate emergency care should be kept in every physician's mind dealing with CBOS., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Limbal Stem Cell Deficiency (LSCD), caused due to corneal injury, primarily by chemical/alkali burns, leads to compromised vision. Recently, several animal models of corneal alkali burn injury have become available. The majority of the studies with these animal models start interventions soon after the injury. However, in the clinical setting, there is a considerable delay before the intervention is initiated. Detailed knowledge of the molecular, histopathological, and clinical parameters associated with the progression of the injury leading to LSCD is highly desirable. In this context, we set out to investigate clinical, histopathological parameters of ocular surface alkali burn over a long period of time, post-injury. Limbal stem cell-deficient animal models of rabbits were created by alkali burn using sodium hydroxide, which was then assessed for their progression towards LSCD by grading the alkali burn, corneal haze, and vascularization. Additionally, cells present on the corneal surface after the burn was investigated by histology and immunophenotyping. Grading of rabbit eyes post-alkali burn had shown complete conjunctivalization in 80% (n = 12/15) of the rabbits with the alkali burn grade score of 3.88 ± 0.29 in three months and remained stable at four months (4.12 ± 0.24). However, ocular surface showed self-healing in 20% (n = 3/15) of the rabbits with a score of 1.67 ± 0.34 in four months irrespective of similar alkali injury. These self-healing corneas exhibited decreased opacity score from 2.51 ± 0.39 to 0.66 ± 0.22 (p = 0.002) and regressed vascularity from 1.66 ± 0.41 to 0.66 ± 0.33 in one to nine months, respectively. Restoration of the corneal phenotype (CK3+) was observed in central and mid-peripheral regions of the self-healing corneas, and histology revealed the localization of inflammatory cells to the peripheral cornea when compared to conjunctivalized and scarred LSCD eyes. Our study shows the essentiality to consider the time required for surgical intervention after the corneal alkali injury in rabbit models as evident from their tendency to self-heal and restore corneal phenotype without therapy. Such information on the possibility of self-healing should be useful in further studies as well as determining interventional timings and strategy during clinical presentation of corneal alkali burns., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal or chemical injury are considered severe ocular surface disorders (OSDs) because they affect the entire ocular surface, including corneal and conjunctival epithelial stem cells. In patients with severe OSDs, the long-term prognosis for limbal transplantation is poor, and the related corneal opacity and cicatrization lead to devastating visual impairment. To date, there is no standardized treatment to improve vision in cases with severe OSD. Investigating novel treatment methods for severe OSDs, our group began cultivated oral mucosal epithelial transplantation in 2002 and developed a limbal-supported rigid-type contact lens that can be applied as a nonsurgical treatment. When used in combination, these treatment methods make it possible to successfully restore vision in cases with severe OSDs.

Purpose: To analyze the protective effect of PARP inhibitors on light-damaged retina and explore its possible mechanism from the perspective of ciliopathy., Methods: A systematic review of the literature was performed to investigate the protection of PARP inhibition on light-damaged cilia. PubMed database was retrieved to find the relevant studies and 119 literatures were involved in the review., Results: In retina, the outer segment of photoreceptor is regarded as a special type of primary cilium, so various retinal diseases actually belong to a type of ciliopathy. The retina is the only central nervous tissue exposed to light, but poly (ADP-ribose) polymerase (PARP), as a nuclear enzyme repairing DNA breaks, is overactivated during the light-induced DNA damage, and is involved in the cell death cascade. Studies show that both ATR and phosphorylated Akt colocalize with cilium and play an important role in regulating ciliary function. PARP may function at ATR or PI3K/Akt signal to exert protective effect on cilia., Conclusion: PARP inhibitors may protect the cilia/OS of photoreceptor during light-induced damage, which the possible mechanism may be involved in the activation of ATR and PI3K/Akt signal.

Introduction: Choking agent exposure, among them chlorine gas, occurs in household or industrial accidents, chemical warfare and terrorist attacks., Aims: Review of published animal and human data regarding the history, pathophysiology, clinical effects and management of chlorine exposure., Pathophysiology: Highly soluble agents cause quick upper respiratory tract symptoms. Chlorine gas has a medium solubility, also causing delayed lower airway symptoms, mainly due to its oxidizing potential by releasing hypochlorous and hydrochloric acid, but also by interacting with Transient Receptor Potential channels., Symptoms: Eyes may show conjunctival injection, abrasions and corrosions. Burns of the oronasal mucosa and trachea can occur. Dyspnea, bronchospasm and possible retrosternal pain occur frequently. Glottis edema or laryngospasm are acute life-threatening emergencies. Chlorine gas can cause toxic pneumonitis, lung edema and acute respiratory distress syndrome (ARDS)., Management: General management includes physical examination, pulse oximetry and arterial blood gases. Eyes should be irrigated, humidified oxygen and inhalative bronchodilators administered. An EKG, cardiac enzymes and complete-blood-count should be obtained if there is retrosternal pain. Routine chest x-ray is not recommended - except if pulmonary edema is suspected. Laryngoscopy should be performed if glottis edema is suspected. Sodium bicarbonate inhalation after chlorine gas inhalation is discussed controversially. Mechanical ventilation with continuous-positive-airway-pressure or intubation/tracheotomy with high positive-end-expiratory-pressure may be necessary. Glucocorticoids for prevention of pulmonary edema should be applied restrictively. Prophylactic antibiotics are not recommended. In severe ARDS, extracorporeal membrane oxygenation (ECMO) can be considered., Conclusion: Treatment is mainly symptom oriented. New and promising therapies are in development., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Wound healing differs significantly between men and women in a tissue-dependent manner. Dermal wounds heal faster in women whereas mucosal wounds heal faster in men. However, the effect of sex as a variable in corneal wound healing is largely unknown. The primary objective of this study was to test whether sex is a biological variable in corneal wound healing activated by the trauma or injury using an established in vivo rabbit model with male and female New Zealand White rabbits. Corneal wounds in rabbits were produced by a single topical alkali (0.5N Sodium hydroxide) application. Serial slit-lamp, stereo biomicroscopy, and applanation tonometry evaluated corneal opacity, anterior segment ocular health, and intraocular pressure (IOP), respectively, at various times during the study. Fourteen days after alkali-wound, corneal tissues were collected after humane euthanasia to examine cellular and molecular wound healing parameters. Quantitative PCR (qPCR) and immunofluorescence were used to quantify changes in the extracellular modeling protein levels of alpha-smooth muscle actin (α-SMA), Fibronectin (FN), Collagen-I (Col-I), and Transforming growth factor beta 1 (TGFβ1) involved in corneal healing. Hematoxylin and Eosin (H&E) staining was used to study histopathological changes in morphology and TUNEL assay to evaluate levels of apoptotic cell death. Male and female rabbits showed no significant differences in corneal opacity (Fantes score) or intraocular pressure (IOP) values (9.5 ± 0.5 mm Hg) in live animals. Likewise, no statistically significant sex-based differences in the mRNA levels of α-SMA (male = 5.95 ± 0.21 fold vs. female = 5.32 ± 0.043), FN (male = 3.02 ± 0.24 fold vs. female = 3.23 ± 0.27), Col-I (male = 3.12 ± 0.37 fold vs. female = 3.31 ± 0.24), TGFβ1 (male = 1.65 ± 0.06 fold vs. female = 1.59 ± 0.053); and protein levels of α-SMA (male = 74.16 ± 4.6 vs. female = 71.58 ± 7.1), FN (male = 60.11 ± 4.6 vs. female = 57.41 ± 8.3), Col-I (male = 84.11 ± 2.8 vs. female = 84.55 ± 3.6), TGFβ1 (male = 11.61 ± 2.8 vs. female = 9.5 ± 3.04) were observed. Furthermore, H&E and TUNEL analyses found no statistically significant differences in cellular structures and apoptosis, respectively, in male vs. female corneas. Consistent with earlier reports, wounded corneas showed significantly increased levels of these parameters compared to the unwounded corneas. Our data suggest that sex is not a major biological variable during active early stages of corneal wound healing in rabbits in vivo., (Copyright © 2019. Published by Elsevier Ltd.)

Purpose: The purpose of this study was to investigate the thermal injuries caused by ultrasonic pars plana phacoemulsification and aspiration (PPPEA) using pig eyes., Method: Using a 20-gauge (G) vitrectomy system (Accurus ® , Fragmatome; Alcon Laboratories) in both the 'open-tip' and 'closed-tip' techniques, PPPEA was performed in pig eyes and the subsequent thermal injuries generated around the scleral wound were measured by infrared thermal imaging (thermography). Post surgery, the state of the scleral wound was observed under a microscope, and a tissue slice containing the scleral wound was then prepared and observed under an optical microscope., Results: Thermography measurements revealed a slight temperature rise around the scleral wound in the open-tip case, yet a marked temperature rise in the closed-tip case. The scleral wound incision produced by the open tip was linear, while that produced by the closed tip was expanded. Histological examination revealed mild degeneration of the sclera around the wound in the open-tip case, yet marked tissue degeneration by thermal injuries in the closed-tip case., Conclusion: Our findings showed that in PPPEA, the temperature of the tip of a 20G vitrectomy system rapidly increases due to the closed-tip technique, thus producing obvious thermal damage to the scleral wound. In order to prevent thermal injuries to the scleral wound during PPPEA, it is important to shorten the time of ultrasonic oscillation during surgery as much as possible while the tip is occluded with nuclear fragments.

Purpose: To compare the outcomes of conventional medical treatment vs combined medical treatment and amniotic membrane transplantation (AMT) in the management of patients with Roper-Hall grade IV ocular chemical injury., Design: Randomized, parallel-controlled clinical trial., Methods: Setting: Single tertiary referral hospital., Patients: Sixty eyes of 60 patients with Roper-Hall grade IV ocular chemical injury with a minimum follow-up of 12 months were enrolled in the study., Intervention: Patients were randomly assigned to 2 groups: Group 1 (30 eyes) received topical preservative-free lubricating gel and drops, chloramphenicol, betamethasone, homatropine, oral vitamin C, and doxycycline; Group 2 (30 eyes) received amniotic membrane transplant (AMT) on the entire ocular surface in addition to the medical treatment provided in Group 1., Outcome Measures: The main outcome measure was time to complete corneal epithelialization. Secondary outcome measures were best-corrected visual acuity (BCVA) and neovascularization in the central 5 mm of the cornea., Results: Mean follow-up time was 20.3 ± 2.5 months (range 13-24 months). Corneal epithelial defects healed within 72.6 ± 30.4 (21-180) days in Group 1 vs 75.8 ± 29.8 (46-170) days in Group 2 (P = .610). Mean BCVA was 2.06 ± 0.67 (0.4-2.6) logMAR vs 2.06 ± 0.57 (1-2.9) logMAR in Groups 1 and 2, respectively (P = .85). Group 1 developed more central corneal neovascularization (22 eyes; 73.3%) compared to Group 2 (16 eyes; 53.3%); however, it was not statistically significant (P = .108)., Conclusions: In comparison to conventional medical therapy, combined amniotic membrane transplantation and medical therapy does not accelerate corneal epithelialization or affect final visual acuity in severe chemical injuries., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To determine the pattern of ocular injuries and their surgical management.., Methods: The retrospective study was conducted at the Chittagong Eye Infirmary and Training Complex, Chittagong, Bangladesh, and comprised hospital data of patients with ocular injuries from October 1, 2016, to December 31, 2017. Information gathered related to type and cause of injuries, visual acuity, postoperative complications, follow-up visits, and outcome. SPSS version 22 was used for data analysis., Results: Of the total injuries, 370 (91%) were classified open globe and 36 (9%) as close globe. In terms of type of injury, 330 (81.4%) were penetrating, 30 (7.3%) ruptured globe, 29 (7.1%) lime burn and 17 (4.2%) injuries were traumatic hyphaema and chemical in nature. Open globe injuries were mostly found in subjects aged 18 years or below. Surgery was the main mode of management in 388 (95.5%) patients., Conclusion: Preventive measures along with high-quality management should receive priority for reducing monocular blindness.

Aims: Cultivated limbal epithelial transplantation (CLET) fails in around 20%-30% of cases. This study aimed to report the clinical outcomes of autologous simple limbal epithelial transplantation (SLET) in eyes with recurrent unilateral limbal stem cell deficiency (LSCD) due to failure of CLET., Methods: This was a prospective case series which included 30 eyes of 30 patients who underwent SLET between 2010 and 2016 after failure of one (n=24) or two (n=6) previous CLET procedures for chronic unilateral ocular burns. The primary outcome measure was success of SLET defined on the basis of relative improvement in five objective criteria: best corrected visual acuity (BCVA), and grades of symblepharon, corneal conjunctivalisation, vascularisation and opacification., Results: At a mean follow-up of 2.3 years, 24 (80%) of the 30 eyes maintained a successful outcome. Kaplan-Meier analysis showed a 5-year survival probability of 77%±8%. At 1 year postoperatively statistically significant improvement was noted in BCVA (logarithm of the minimum angle of resolution of 3 to 1) and in the median grades of corneal conjunctivalisation (2 to 0), vascularisation (2 to 0) and opacification (2 to 1) (P≤0.0026). In 62.5% of successful cases, BCVA improved to 20/200 or better. The success rate of SLET in failed CLET was better than that of repeat CLET (53.5%, P=0.011). None of the donor eyes developed any complications., Conclusion: SLET is an effective alternative to CLET in eyes with recurrence of LSCD after previously failed CLET procedures. Since SLET is single-staged and less expensive, it is probably preferable to repeating CLET., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To describe the technique and present 2 cases of a combined conjunctival limbal autograft (CLAU) and living-related conjunctival limbal allograft (lr-CLAL) procedure for treatment of severe unilateral ocular surface failure., Methods: Interventional case series of 2 eyes of 2 patients sustaining severe thermal/chemical injuries from firework explosions. They both underwent the combined CLAU/lr-CLAL procedure followed by penetrating keratoplasty. Systemic immunosuppression consisted of oral tacrolimus and mycophenolate mofetil., Results: Preoperative vision was counting fingers for both patients, whereas visual acuity at last follow-up ranged between 20/40 and 20/50. Both patients maintained a stable surface at last follow-up without any episodes of rejection. Patients tolerated systemic immunosuppression well without any persistent adverse reactions., Conclusions: Certain etiologies of limbal stem cell deficiency also lead to significant conjunctival (and goblet cell) deficiency. Combined CLAU and lr-CLAL procedures maximize the amount of healthy limbal stem cells with conjunctiva while also minimizing the antigenic burden as all transplanted tissue potentially can be a complete (or near-complete), compatible HLA and crossmatch.

Significance: Ocular chemical injury is a medical emergency in which immediate treatment is critical to prevent visual morbidity. We report a severe ocular burn case that illustrates in-office management to promote rapid re-epithelialization and reduce inflammation to restore ocular surface integrity., Purpose: To report a case of severe acid burn that was managed successfully with self-retained cryopreserved amniotic membrane (AM)., Methods: A 43-year-old man presented with complaints of pain, light sensitivity, and blurred vision in both eyes 1 day after ocular exposure to acid. Symptoms and signs were more severe in the left eye. Examination revealed diffuse conjunctival inflammation and extensive corneal, conjunctival, and limbal epithelial defects in the left eye; hence, application of cryopreserved AM was performed., Results: Placement of three self-retained AMs over a 10-day period resulted in resolution of symptoms, reduction in inflammation, complete re-epithelialization of corneal and limbal defects, and improvement of visual acuity from 20/50 to 20/20. Intriguingly, areas of conjunctival inflammation not covered by the AM remained inflamed., Conclusions: In this case of acute chemical burn, application of self-retained AM 24 hours after injury was effective in promoting ocular surface healing, reducing inflammation, and restoring visual acuity.

Purpose: To explore whether alkali burn causes corneal neuropathic pain and activates the neuropathic pain matrix in the central nervous system in mice., Methods: A corneal alkali burn mouse model (grade II) was used. The mechanical threshold in the cauterized area was tested using Von Frey hairs. Spontaneous pain behavior was investigated with conditioned place preference. Phosphor extracellular signal-regulated kinase (ERK), which is a marker for neuronal activation in chronic pain processing, was investigated in several representative areas of the neuropathic pain matrix: the 2 regions of the spinal trigeminal nucleus (subnucleus interpolaris/caudalis, Vi/Vc; subnucleus caudalis/upper cervical cord, Vc/C1), insular cortex, anterior cingulated cortex (ACC), and the rostroventral medulla (RVM). Furthermore, pharmacologically blocking pERK activation in the ACC of alkali burn mice was performed in a separate study., Results: Corneal alkali burn caused long-lasting damage to the corneal subbasal nerve fibers, and mice exhibited spontaneous pain behavior. By testing in several representative areas of the neuropathic pain matrix in the higher nervous system, phosphor ERK was significantly activated in Vc/C1, but not in Vi/Vc. Also, ERK was activated in the insular cortex, ACC, and RVM. Furthermore, pharmacologically blocking ERK activation in the ACC abolished alkali burn induced corneal spontaneous pain., Conclusions: Alkali burn could cause corneal spontaneous pain and activate the neuropathic pain matrix in the central nervous system. Furthermore, activation of ERK in the ACC is required for alkali burn induced corneal spontaneous pain.

Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO 2 ) on corneal wound healing. We found that NaNO 2 (0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO 2 (10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.

The paper presents an atypical case of solar retinopathy after short-term exposure to reflected focused sunbeams. An ophthalmoscopic peculiarity was the presence of intraretinal hemorrhage. The basis for establishing the diagnosis were spectral optical coherence tomography and fluorescein angiography findings.

Purpose: To evaluate the influence of somatostatin (SST) and its analog octreotid (Oct) on corneal wound healing processes., Methods: The wound healing rate in C57BL/6 mice eyes under SST and Oct treatment was analyzed using an alkali-induced corneal wounding model. Effects of SST and Oct on cell proliferation, migration and quantified protein expression of vascular endothelial growth factor (VEGF) on human corneal epithelial cells (HCE, cell line) were evaluated by means of electric cell-substrate impedance sensing, scratch migration assays and ELISA. ERK1/2 and p38 phosphorylation was investigated by semi-quantitative western blot analysis., Results: Ten nanograms per microliters of SST significantly accelerated the wound closure rate of corneal defects in vivo. SST and Oct had no influence on HCE cell proliferation and migration and did not activate ERK1/2 or p38 signaling in HCE cells. However, there was increased VEGF protein expression in cytosolic proteins and medium supernatants of HCE upon Oct stimulation for 24h. One and 10ng/ml Oct led to a 2.5-fold and 100ng/ml Oct to a 4-fold upregulation of VEGF protein expression., Conclusion: The data implicate that SST promotes corneal wound healing in a mouse model. However, using a HCE cell line in vitro, the wound healing mechanism does not seem to be supported by proliferation and migration processes or by activation of ERK1/2 and p38 signaling pathways. Other possible mechanisms could be the activation of other pathways and the induction of growth factors such as VEGF that modulate the observed corneal wound healing process., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Purpose: To report the clinical course of a patient sustaining a ocular laser injury from 1,064-nm Nd:YAG cosmetic laser machine., Method and Patient: A 31-year-old beauty parlor aesthetician was operating an Nd:YAG cosmetic laser machine of 1,064 nm wavelength. However, the probe was held in the opposite direction, and on firing, the laser shot fired into her left eye. The patient heard a "pop" sound followed by immediate floaters and blurring of vision. Her clinical course was followed for 6 weeks, with investigations including optical coherence tomography, fluorescein angiogram, and Humphrey's visual field examination performed., Results: Optical coherence tomography taken over the injured area showed thickened retina and preretinal hyperreflectivities. Fluorescein angiogram showed hypofluorescence superonasal to the disk with late staining of vessels. Humphrey's visual field showed a dense scotoma emanating from the blind spot. The lesion eventually scarred down, and the patient's vision recovered., Discussion: The eye is the most susceptible body part to laser light injury. A review of reported laser accidents revealed the majority to be ocular injuries. The retina is particularly vulnerable, as laser light with wavelength between 400 nm and 1,400 nm is focused by the cornea and lens onto the retina, increasing the retinal irradiance as a result. Most injuries were parafoveal, suggesting that most injuries occurred during laser beam alignment. The prognosis is generally favorable. As laser use becomes more widespread and its application increasingly heterogeneous, regulation of laser use and monitoring of laser safety are crucial but at the same time challenging.

Objective: The aim of this study was to evaluate the clinical outcomes of the implantation of MICOF keratoprosthesis (Kpro) in patients with alkaline, acid and thermal ocular burns., Methods: This is a retrospective, non-competitive, interventional case series. Ninety eyes of 90 patients with ocular burns underwent MICOF KPro surgery at the Chinese People's Liberation Army General Hospital between April 2000 and December 2012. Preoperative and postoperative findings were recorded. Retention of the prostheses and the treatment for postoperative complications were investigated., Results: The mean age of patients was 40.26±12.18 years (range: 8-64 years), and the mean duration after ocular trauma was 4.8±6.2 years (range: 1.5-12 years). The mean follow-up period was 58.22±36.28 months (range: 1-145 months). Eighty patients were followed for ≥1 year and 73 eyes (81.11%) achieved the best-corrected visual acuity of 20/200 or better and 39 eyes (43.33%) achieved best-corrected visual acuity of ≥20/40. The common complications were glaucoma, corneal melt and conjunctiva overgrowth, and the incidences of these complications were 59.99%, 40% and 31.11%, respectively. One patient experienced KPro extrusion, and two patients exhibited leakage from the area of the implant. Seven with endophthalmitis eyes had final visual acuities of light perception. There was no significant difference in the effectiveness of the implants among the different causes of injuries, including acid, alkali and thermal burns., Conclusions: MICOF Kpro is an effective alternative for patients with ocular burn with corneal blindness. Glaucoma and endophthalmitis were identified as significant risk factors for visual loss., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial., (© 2015 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc.)

Purpose: To evaluate the efficacy of mesenchymal stem cells (MSCs) to ameliorate the consequences of corneal alkali injuries., Methods: Corneal alkali injuries were created in 30 rabbit eyes. The MSC group (n = 15) were treated with intrastromal and subconjunctival injections of phosphate-buffered saline (PBS) containing 2 × 10(6) MSCs and topical application. The control group (n = 15) was treated with PBS by the same applications forms. Drops of standard treatment (ascorbate 10 %, citrate 10 %, tobramycin, dexamethasone, Cyclogyl) were instilled for 2 weeks. Rabbits underwent slit-lamp examination, fluorescein staining, photography, and were evaluated for corneal neovascularization, opacification, and epithelial defects. Tear secretion and IOP were also evaluated. Furthermore, the concentration of Serumglutamic-pyruvic transaminase (SGPT) and vascular endothelial factor (VEGF) were measured. Immunohistochemistry was also performed for a-SMA and Ki-67., Results: Eyes treated with MSCs showed better recovery. The mean neovascularized area was significantly smaller in the MSC group (p < 0.05). A significant difference in the degree of corneal opacification and re-epithelialization was also observed, as well as the IOP at 21 and 28 posttraumatic days (p < 0.05). Histology showed that MSCs resulted in almost normal architecture of eye tissues. After the MSCs infusion, SGPT and VEGF levels in cornea were significantly reduced. Immunohistochemistry demonstrated a reduction of a-SMA in the MSC group with higher mitotic-regenerative activity with the presence of Ki67., Conclusions: Our study represents a first step in understanding the possibilities of the MSC approach to treatment of alkali injuries of the cornea and shows that such an approach improves clinical outcomes and leads to better prognosis.

We examined whether the loss of transient receptor potential ankyrin 1 (TRPA1), an irritant-sensing ion channel, or TRPA1 antagonist treatment affects the severity inflammation and scarring during tissue wound healing in a mouse cornea injury model. In addition, the effects of the absence of TRPA1 on transforming growth factor β1 (TGF-β1)-signaling activation were studied in cell culture. The lack of TRPA1 in cultured ocular fibroblasts attenuated expression of TGF-β1, interleukin-6, and α-smooth muscle actin, a myofibroblast the marker, but suppressed the activation of Smad3, p38 MAPK, ERK, and JNK. Stroma of the healing corneas of TRPA1(-/-) knockout (KO) mice appeared more transparent compared with those of wild-type mice post-alkali burn. Eye globe diameters were measured from photographs. An examination of the corneal surface and eye globes suggested the loss of TRPA1 suppressed post-alkali burn inflammation and fibrosis/scarring, which was confirmed by histology, immunohistochemistry, and gene expression analysis. Reciprocal bone marrow transplantation between mice showed that KO corneal tissue resident cells, but not KO bone marrow-derived cells, are responsible for KO mouse wound healing with reduced inflammation and fibrosis. Systemic TRPA1 antagonists reproduced the KO phenotype of healing. In conclusion, a loss or blocking of TRPA1 in mice reduces inflammation and fibrosis/scarring in the corneal stroma during wound healing following an alkali burn. The responsible mechanism may include the inhibition of TGF-β1-signaling cascades in fibroblasts by attenuated TRPA1 signaling. Inflammatory cells are considered to have a minimum involvement in the exhibition of the KO phenotype after injury.

Alkali burns are known to possess high pathological potential because of their inherent ability to lyse cell membranes and penetrate intraocular structures with devastating results. The authors aimed to evaluate the most common cause of this presentation, the current treatment approaches to injury, and eventual outcome as related to severity. The authors performed a retrospective review of all patients who sustained chemical-related ocular injuries seen at the Concord Hospital Burns Unit, Australia between January 2005 and March 2012. Management was based on cooperation between ophthalmic staff and the burns unit, with emphasis on early aggressive intervention and rigorous follow-up. The records of 39 patients who presented with chemical-related injury were assessed, 12 of whom had confirmed alkali burns involving the cornea. The most commonly implicated agent was sodium hydroxide, usually in the context of otherwise trivial domestic accidents. Acute medical management included copious irrigation and the use of analgesics, cycloplegics, and topical antibiotics. In half the cases, steroid drops and oral vitamin C were also used. Ten of the 12 patients (83%) had return to premorbid visual acuity. Complications included cicatrical ectropion (n = 1), pseudoexfoliative syndrome (n = 1), and symblepharon (n = 1). Surgical correction was needed in the one patient with cicatrical ectropion. This case series shows that appropriate acute management minimizes the potentially devastating sequelae of ocular alkali burns. Emphasis should be placed on prevention of domestic and workplace injuries when using alkaline products.

Clinical patterns of ocular burn in patients with different types and variants of stress reactivity were studied. It is shown that patients with the maladaptive type of stress reactivity at any stage of the disease are at higher risk of complications. Rapid exhaustion of the sympathoadrenal system or a hyperactive stress response seen in cases of the labile and hyperergic individual adrenergic immune reactivity of the organism (IAIRO) can be considered as manifestations of a regulation disorder. The absence of complications along with mild changes in immune reactivity is characteristic of the normoergic variant of IAIRO.

Importance: Although several reports are available on the use of conventional and cultured limbal epithelium using various substrates in the treatment of limbal stem cell deficiency (LSCD), the patient populations studied have been largely adults. Thus, to our knowledge, the outcomes of this procedure exclusively in a pediatric population have not been reported previously., Objective: To report the outcomes of autologous ex vivo cultivated limbal epithelial transplantation (CLET) in pediatric patients with LSCD after ocular burns., Design and Setting: A retrospective, interventional case series of patients treated at the L. V. Prasad Eye Institute, Hyderabad, India., Participants: Children up to 15 years with LSCD secondary to chemical or thermal injury who underwent CLET from April 1, 2001, through June 31, 2010, with a follow-up of at least 1 year, were included in the study., Intervention: After a limbal biopsy specimen obtained from a healthy area of the limbus, the limbal epithelial cells were cultured on a denuded human amniotic membrane substrate using a xeno-free explant culture technique. A monolayer of cultivated epithelial cells along with the amniotic membrane was transplanted on the patient's affected eye after pannus excision. In cases of failure, the same procedure was repeated., Main Outcomes and Measures: Ocular surface stability and visual improvement were the primary and secondary outcome measures, respectively. Success was defined as a stable corneal epithelium without conjunctivalization. Eyes with conjunctivalization and persistent epithelial defects were classified as failures., Results: Of the 107 eyes of 107 patients included in this study, 73 eyes (68.2%) underwent 1 and 34 eyes (31.8%) underwent 2 autologous CLET procedures. At a mean follow-up of 3.4 years, 50 eyes (46.7%) achieved completely epithelialized, avascular, and stable ocular surfaces. At the final visit, 58 eyes (54.2%) had improvement in visual acuity of 0.2 or more logMAR units., Conclusions: Autologous CLET was successful in restoring the ocular surface and improving vision in almost half of the children blinded by ocular burns.

Purpose: Adipose-derived stem cells (ADSC) are multipotent, safe, non-immunogenic and can differentiate into functional keratocytes in situ. The topical use of ADSC derived from human processed lipoaspirate was investigated for treating injured rat cornea., Methods: A total of 19 rats were used. Six animals initially underwent corneal lesion experiments with 0.5 N NaOH (right eye) and 0.2 N (left). The 0.2 NaOH protocol was then used in 13 rats. All 26 eyes of 13 rats eyes received topical azythromycin bid for 3 d and divided into five treatment groups (n = 5 eyes/group), which included: control, stem cells, serum, stem + serum and adipose (raw human lipoaspirate). The four treatment groups received topical treatment three times daily for 3 d. Stem cells were isolated and harvested from human lipoaspirate. Topical eye drops were prepared daily with 1 × 10(5) cells/treatment. Fluorescein positive defect area and light microscope assessment was performed at 20, 28, 45, 50 and 74 h. Animals were sacrificed at 74 h for histological evaluation. Data were statistically analyzed for differences amongst groups., Results: The stem cell-treated eyes had significantly smaller epithelial defects at each time point compared to control- and adipose-treated eyes (p < 0.05). This group showed slightly better epithelium healing than the serum and combined group, yet not significantly different. Histology showed that stem cell-treated corneas had complete re-epithelization, with less inflammatory cells and limited fibroblast activation structure compared with the control eyes., Conclusions: Our preliminary results show that topical treatment with ADSC seems to improve corneal wound healing.

A case report highlighting an unusual cause of a chemical injury and an explanation of the basic initial management of chemical eye injuries: relevant to all Armed Forces medical personnel.

Purpose: To describe the clinical course, ultrasonographic and confocal microscopic findings in a patient who developed a large Descemet membrane (DM) detachment that resolved spontaneously after ocular sodium cyanide injury., Methods: Case report., Results: The patient presented with severe corneal stroma edema, a large detachment of DM, iritis, and anterior subcapsular lens opacity in the left eye caused by contact with 5% sodium cyanide. The ultrasound biomicroscopic and in vivo confocal microscopic examination exhibited the configuration of the DM detachment and extensive damage of corneal cells. Although no viable endothelial cells were observed with in vivo confocal microscopy, the DM spontaneously reattached 11 days after injury, coincident with increased intraocular pressure. However, persistent corneal edema and iris atrophy were observed 6 months after DM reattached., Conclusions: Sodium cyanide can cause severe injuries to the cornea and the anterior segment. Extensive DM detachment may resolve spontaneously despite the absence of viable endothelial cells.

Purpose: To determine the indications and outcomes of Boston type 1 keratoprosthesis (Massachusetts Eye and Ear Infirmary, Boston, MA) surgery performed outside of North America and to compare them with those obtained in the United States by the surgeon who trained the international surgeons., Design: Retrospective review of consecutive clinical case series., Participants: One hundred ninety-four patients (223 keratoprosthesis procedures performed in 205 eyes) who received Boston type 1 keratoprosthesis at 11 ophthalmology centers in Armenia, India, Indonesia, Nepal, Philippines, Russia, and Saudi Arabia between May 1, 2006, and July 1, 2011 (international series), and at the Jules Stein Eye Institute between May 1, 2004, and July 1, 2011 (University of California, Los Angeles [UCLA] series)., Methods: Data were collected for each procedure regarding the preoperative characteristics of each eye, the surgical procedure(s) performed, and the postoperative outcomes. Statistical analysis was performed to identify significant differences between the international and UCLA series in terms of retention and complications., Main Outcome Measures: Interval visual acuities, keratoprosthesis retention, and significant postoperative complications., Results: In the international series, 113 Boston type I keratoprostheses were implanted in 107 eyes of 100 patients. The most common indication for surgery was corneal graft failure (n = 50; 44%) followed by chemical injury (n = 30; 27%). Although only 2% of eyes had a preoperative corrected distance visual acuity (CDVA) of 20/20 to 20/200, 70%, 68%, and 59% of eyes had a postoperative CDVA of 20/20 to 20/200 at 6 months, 1 year, and 2 years after surgery, respectively. Ninety-one of the 113 keratoprostheses implanted (80.5%) were retained at a mean follow-up of 14.2 months, for a retention failure rate of 22 per 134.6 eye-years (0.163/eye-year). The most common postoperative complications were retroprosthetic membrane formation (27%) and sterile corneal necrosis (18%). The only postoperative complication that was more common in the international series than in the UCLA series was infectious endophthalmitis, which developed in 9% of eyes., Conclusions: Boston keratoprosthesis is a viable means of managing repeat graft failure and ocular chemical injury outside of North America, with similar visual acuity outcomes, retention rates, and incidence rates of postoperative complications to those obtained by North American surgeons., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Increased plasminogen level in tear fluid was found within 28 days and increased plasmin activity in 1-3 and 21 days after alkali burn of cornea, this is the time of cornel ulcers development. Increased plasminogen level and plasmin activity in cornea, conjunctiva and intraocular fluid was found in three days after trauma. Subconjunctival injections of angiostatin K1-4,5 (a product of plasminogen metabolism) during 3 weeks resulted in significant suppression of corneal neovascularization within 14 days and of active branching of the vessels in the following. The use of angiostatin reduced depth and area of corneal ulcers. Obtained data shows the promising potential of development of medications based on angiostatin K1-4,5 for suppression of corneal neovascularization and for treatment of diseases associated with corneal ulceration.

This study describes a novel surgical technique of limbal transplantation, which combines the benefits of existing techniques while avoiding their difficulties. Six patients with unilateral and total limbal stem cell deficiency following ocular surface burns underwent a single-stage procedure. A 2 × 2 mm strip of donor limbal tissue was obtained from the healthy eye and divided into eight to ten small pieces. After surgical preparation of the recipient ocular surface, these tiny limbal transplants were distributed evenly over an amniotic membrane placed on the cornea. After surgery, a completely epithelialised, avascular and stable corneal surface was seen in all recipient eyes by 6 weeks, and this was maintained at a mean ± SD follow-up of 9.2 ± 1.9 months. Visual acuity improved from worse than 20/200 in all recipient eyes before surgery to 20/60 or better in four (66.6%) eyes, while none of the donor eyes developed any complications. This technique requires less donor tissue than previously used for conventional autografting and does not need a specialist laboratory for cell expansion. Although long-term results are awaited, this simple limbal epithelial transplantation promises to be an easy and effective technique for treating unilateral limbal stem cell deficiency following ocular burns.

Purpose: To report the clinical outcomes of repeat autologous cultivated limbal epithelial transplantation in patients with recurrence of limbal stem cell deficiency after a failed primary procedure., Design: Retrospective case series., Methods: This study included 50 patients, above 8 years of age, with clinically diagnosed unilateral limbal stem cell deficiency following ocular surface burns, treated between 2001 and 2010. Following failure of primary surgery all patients underwent a repeat limbal biopsy from the unaffected eye. The limbal cells were expanded ex vivo on a human amniotic membrane substrate for 10 to 14 days using a completely xeno-free explant culture technique. The resulting cultured epithelial monolayer and amniotic membrane were transplanted onto the patient's affected eye. All patients underwent a comprehensive ophthalmic examination of both eyes at every follow-up visit. Postoperative corneal surface stability, change in visual acuity, and complications were objectively analyzed., Results: At a mean follow-up of 2.3±1.4 (median: 1.96, range: 1 to 7.5) years, 33 of the 50 recipient eyes (66%) maintained a completely epithelialized, avascular, and clinically stable corneal surface. A 2-line improvement in visual acuity was seen in 38 of the 50 recipient eyes (76%). None of the donor eyes developed any clinical features of ocular surface disease, conjunctival overgrowth of the donor site, or decrease in vision throughout the follow-up period., Conclusions: Repeat autologous cultivated limbal epithelial transplantation successfully restores corneal epithelial stability and improves vision in eyes with recurrence of limbal stem cell deficiency, following failed primary surgery for ocular burns, without adversely affecting donor eyes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cellular senescence acts as a potent regulator of tumor suppression and fibrosis limitation; however, its contribution and crosstalk with neovascularization during normal wound healing has not been examined. Here, we explored the role of senescent fibroblasts on neovascularization with a mouse model of alkali-induced corneal wound healing. Senescent cells accumulated in corneal stroma from day 7 to 27 after alkali burn and peaked on day 14, which was consistent with the development of corneal neovascularization (CNV). In vitro and in vivo assays confirmed that the senescent cells were derived primarily from activated corneal fibroblasts. Furthermore, senescent corneal fibroblasts exhibited enhanced synthesis and secretion of extracellular matrix-degrading enzymes (matrix metalloproteinases 2, 3, and 14 and tissue- and urokinase-type plasminogen activators) and angiogenic factors (vascular endothelial growth factor) and decreased expression of anti-angiogenic factors (pigment epithelium-derived factor and thrombospondins), which supported the proliferation, migration, and promotion of tube formation of vascular endothelial cells. Intrastromal injection of premature senescent fibroblasts induced CNV earlier than that of normal fibroblasts, while matrix metalloproteinase inhibitors blocked the early onset of senescent cell-induced CNV. Therefore, senescent fibroblasts promoted the alkali-induced CNV partially via the enhanced secretion of matrix metalloproteases., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: To report the use of the Boston Ocular Surface Prosthesis (BOSP) in patients with severe periorbital thermal injuries., Design: Retrospective, interventional case series., Participants: Patients with severe periorbital thermal injuries treated with the BOSP., Methods: Chart review of 10 consecutive patients (16 eyes) who sustained severe periorbital thermal injuries during combat missions in Iraq and Afghanistan and were treated for exposure keratopathy with the BOSP, a Food and Drug Administration-approved gas-permeable, scleral contact lens., Main Outcome Measures: Corneal epithelial defect healing, uncorrected and best-corrected visual acuity, and BOSP wear time., Results: Exposure keratopathy occurred after severe periorbital thermal injuries and followed a predictable course of scar contracture. In all patients, vision-threatening ocular surface disease developed as a result of chronic ocular exposure. Rehabilitation of the ocular surface was accomplished using the BOSP, with 10 of the 16 treated eyes achieving a corrected visual acuity of 20/70 or better. Five eyes achieved a best-corrected visual acuity of 20/40 or better. The BOSP also was used as a drug-delivery vehicle to treat corneal ulcers successfully in 6 eyes. The only eye that required penetrating keratoplasty was an early intervention believed to be a direct sequelae of the original thermal burn, rather than a failure of the BOSP regimen. The mean BOSP wear time was 16 hours per day., Conclusions: The BOSP can play an important role in rehabilitation of the ocular surface for patients with severe periorbital thermal injuries and resultant exposure keratopathy. Use of the BOSP should be considered as a treatment option for these difficult cases of severe periorbital thermal injuries., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The peroxisome proliferator-activated receptor (PPAR) δ is involved in tissue repair. In this study, we investigated the functional role of PPARδ in corneal epithelial wound healing. In an in vivo corneal wound-healing model, the changes of PPARδ expression in corneal epithelia were examined by immunofluorescence microscopy, and the effect of topical administrations of a PPARδ agonist on corneal wound healing was also evaluated. The inhibitory effect of a PPARδ agonist on the cytokine-induced death of human corneal epithelial cells was evaluated using a DNA fragmentation assay kit. The changes of PPARδ expression and epithelial cell death were also investigated using human corneoscleral tissues ex vivo. Our findings showed that PPARδ expression was temporally up-regulated in corneal epithelial cells during experimental wound healing and that topical administration of a PPARδ agonist significantly promoted the healing of experimental corneal epithelial wounds. In human corneal epithelial cells, up-regulation of PPARδ and DNA fragmentation was demonstrated by stimulation with cytokines, and the DNA fragmentation was significantly inhibited by pretreatment with a PPARδ agonist. By using human corneoscleral tissues ex vivo, PPARδ was up-regulated in both healthy corneal epithelia (during re-epithelialization) and diseased corneal epithelia. Inflammatory stimulation-induced corneal epithelial cell death was inhibited by pretreatment with a PPARδ agonist. These results strongly suggest that PPARδ is involved in the corneal epithelial wound healing., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The extraction residue of the Ganoderma fruiting body, named sacchachitin, has been demonstrated to have the potential to enhance cutaneous wound healing by inducing cell proliferation. In this study, a nanogel formed from micronized sacchachitin (mSC) was investigated for the potential treatment of superficial chemical corneal burns. Reportedly, mSC has been produced successfully and its chemical properties confirmed, and physical and rheological properties characterized. An in vitro cell proliferation study has revealed that at the concentrations of 200, 300, and 400 microg/mL, mSC nanogel significantly increased Statens Seruminstitut rabbit corneal (SIRC) cell proliferation after 24 hours of incubation. In cell migration assay, migration of SIRC cell to wound closure was observed after 24 hours of incubation with the addition of 200 microg/mL mSC of nanogel. In an animal study, acceleration of corneal wound healing was probably due to the inhibition of proteolysis. In conclusion, the findings of this study substantiate the potential application of sacchachitin in the form of mSC nanogel for the treatment of superficial corneal injuries.

Purpose: To report the clinical outcomes of penetrating keratoplasty (PK) after autologous cultivated limbal epithelial transplantation in eyes with limbal stem cell deficiency (LSCD) after ocular surface burns., Design: Retrospective case series., Methods: This study included 47 patients with unilateral LSCD treated by autologous cultivated limbal epithelial transplantation and PK between 2001 and 2010. PK was performed either along with (single-stage; n = 12) or at least 6 weeks after (2-stage; n = 35) limbal transplantation. The primary outcome measure was corneal allograft survival, and failure was defined clinically as loss of central graft clarity. Secondary outcomes were postoperative Snellen visual acuity and complications., Results: Most patients were young (mean age, 18 ± 11.4 years) males (76.6%) with LSCD resulting from alkali burns (78.7%) and with visual acuity less than 20/200 (91.5%). The mean follow-up was 4.2 ± 1.9 years. Kaplan-Meier corneal allograft survival rate at 1 year was significantly greater in eyes undergoing 2-stage limbal and corneal transplantation (80 ± 6%; median survival, 4 years) compared with single-stage limbal and corneal transplantation (25 ± 13%; median survival, 6 months; P = .0003). Visual acuity of 20/40 or better was attained by 71.4% of eyes with clear corneal grafts. Allograft failure occurred in 26 (60.5%) eyes as a result of graft rejection (57.7%), graft infiltrate (26.9%), or persistent epithelial defects (15.4%). Recurrence of LSCD was more common after single-stage (58.3%) than 2-stage (14.3%) surgery (P = .008)., Conclusions: The 2-stage approach of autologous cultivated limbal epithelial transplantation followed by PK successfully restores ocular surface stability and vision in eyes with chronic ocular burns. The single-stage approach is associated with poorer clinical outcomes and should be avoided., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To report the clinical outcomes of lamellar keratoplasty (LKP) in patients with delayed-onset mustard gas keratitis and to compare visual acuity and graft survival rates between subgroups with simultaneous or sequential keratolimbal allograft and LKP., Design: Retrospective, comparative, interventional case series., Methods: Fifty-two eyes of 37 male survivors of chemical warfare with mustard gas keratitis who underwent LKP were included. The results were evaluated with respect to best spectacle-corrected visual acuity (BSCVA), refractive error and keratometry readings, and graft clarity. Thirty-two eyes required stem cell transplantation (keratolimbal allograft), which was performed before or concomitant with LKP. The groups with sequential and concomitant intervention were compared regarding BSCVA, refraction, corneal graft surface stability, and stem cell and corneal graft survival rates., Results: The mean patient age at the time of surgery was 43.4 ± 8.2 years, and the mean follow-up period was 41.4 ± 19.6 months. The mean preoperative BSCVA was 0.51 ± 0.48 logarithm of the minimal angle of resolution units, which increased to 0.33 ± 0.18 logarithm of the minimal angle of resolution units (P = .03). The mean preoperative spherical equivalent refractive error was -2.40 ± 1.5 diopters, which remained unchanged after surgery (-1.52 ± 3.7 diopters; P = .77). No significant difference between the sequential and simultaneous subgroups was found with regard to postoperative BSCVA, refraction, keratometry readings, or corneal graft survival (90.3% and 89.9%, respectively; P = .68). However, the latter group had statistically better stem cell graft survival (40.0% vs 100% at month 41, respectively; P = .02)., Conclusions: LKP is an effective method of corneal transplantation in mustard gas victims. When stem cell and corneal transplantation are indicated, the simultaneous approach can yield better results than staged intervention., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess vision-related quality of life in patients with ocular chemical burns by the application of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25)., Methods: Eighty-seven patients with ocular chemical burns were enrolled in the study from January 1 through May 31, 2010. Apart from the collection of sociodemographic and clinical data, NEI VFQ-25 with an additional appendix question, being translated to Chinese, was administered to all subjects. Main outcome measures were comparison of the NEI VFQ-25 subscale item scores among subgroups and multivariate analysis of the NEI VFQ-25 subscale scores., Results: Fifty-five subjects were bilaterally burned and the rest were unilaterally injured. The mean age of enrolled subjects was 39.4 ± 11.6 years, with the majority being male (98.9%) and worker (77.0%); the mean composite score of all subjects was 40.4 ± 23.8. The composite score and majority subscale scores of binocularly injured patients were significantly lower than those of monocularly injured patients. Further comparisons among groups divided by either clinical severity classification or best-corrected visual acuity (BCVA) produced similar results. The BCVA of both the better-seeing eye and the worse-seeing eye strongly correlated with the NEI VFQ-25 composite score (ρ = 0.664 and 0.498, both P = 0.000). Multivariate regression analysis revealed that the VFQ-25 composite score correlated significantly with the following independent variables: BCVA of the better-seeing eye and the worse-seeing eye, the injury classification of the less severely injured eye, and correct and immediate irrigation after injury as well., Conclusions: Ocular chemical burns have a significant and extensive impact on patients' visual function outcomes and vision-related quality of life.

Purpose: Ocular burns can damage the corneal epithelial stem cells located at the limbus. This study evaluated the efficacy of xeno-free autologous cell-based treatment of limbal stem cell deficiency., Methods: This retrospective study included 200 patients, above 8 years of age, with clinically diagnosed unilateral total limbal stem cell deficiency due to ocular surface burns treated between 2001 and 2010. A small limbal biopsy was obtained from the unaffected eye. The limbal epithelial cells were expanded ex vivo on human amniotic membrane for 10-14 days using a xeno-free explant culture system. The resulting cultured epithelial monolayer and amniotic membrane substrate were transplanted on to the patient's affected eye. Postoperative corneal surface stability, visual improvement and complications were objectively analysed., Results: A completely epithelised, avascular and clinically stable corneal surface was seen in 142 of 200 (71%) eyes at a mean follow-up of 3 ± 1.6 (range: 1-7.6) years. A two-line improvement in visual acuity, without further surgical intervention, was seen in 60.5% of eyes. All donor eyes remained healthy., Conclusions: Autologous cultivated limbal epithelial transplantation using a xeno-free explant culture technique was effective in long-term restoration of corneal epithelial stability and improvement of vision in eyes with ocular surface burns.

Purpose: To determine whether deep anterior lamellar keratoplasty (DALK) using acellular glycerol-cryopreserved corneal tissue (GCCT) could prevent allograft rejection in high-risk corneas., Design: Prospective, randomized, comparative study., Settings: The Eye Hospital, Wenzhou Medical College, Zhejiang, China., Study Population: All patients with herpes simplex virus keratitis, bacterial keratitis, fungal keratitis, or ocular burn, who were eligible as per study design, were invited to participate., Observation Procedures: According to randomized block design, all patients received either GCCT or fresh corneal tissue (FCT) during DALK. Best-corrected visual acuity (BCVA), slit-lamp microscopy, and in vivo confocal microscopy examinations at 1 week and 1, 3, 6, 12, and 24 months after surgery were analyzed. Kaplan-Meier survival analysis was used to evaluate graft survival rate., Main Outcome Measures: Therapeutic success, 2-year rejection-free graft survival rate and 2-year graft survival rate, in vivo confocal microscopy results, BCVA, and endothelial cell density., Results: Postoperative BCVA of 20/40 or better at the last follow-up visit was achieved in 57.6% (19/33) of eyes in the GCCT group and in 54.8% (17/31) of the FCT group. No graft rejection occurred in the GCCT group, while in the FCT group 10 episodes of stromal rejection developed in 7 eyes. Overall, the rejection-free graft survival rate at 2 years was significantly higher in the GCCT group as compared with the FCT group (100.0%, 78.8% respectively, P = .006)., Conclusions: Deep anterior lamellar keratoplasty using acellular glycerol-preserved cornea could prevent allograft rejection and promote graft survival rate in high-risk corneas., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims: To evaluate the role of amniotic membrane transplantation in patients with acute ocular burns., Methods: In a prospective, randomised, controlled clinical trial, 100 patients with grade II to IV acute ocular burns (Roper Hall Classification) were recruited. 50 patients with grade II-III burns were graded as moderate burns, and 50 patients with grade IV burns were graded as severe burns. Both groups were individually randomised into control group (n=25) and study group (n=25). The corresponding grade of ocular surface burn by Dua classification was noted. The eyes in the study group underwent amniotic membrane transplantation in addition to conventional medical therapy. In the control group, conventional medical therapy along with mechanical release of early adhesions as and when necessary was instituted. Rate of healing of corneal epithelial defect, visual acuity, extent of corneal vascularisation, corneal clarity and formation of symblepharon were compared in both groups., Results: In patients with moderate ocular burns treated with amniotic membrane transplantation, the rate of epithelial healing was significantly better than the group treated with standard medical therapy alone (p=0.0004). There was no overall difference in the final visual outcome, symblepharon formation, corneal clarity and vascularisation with or without amniotic membrane transplantation., Conclusions: Amniotic membrane transplantation in eyes with acute ocular burns promotes faster healing of epithelial defect in patients with moderate grade burns. There seems to be no definite long-term advantage of amniotic membrane transplantation over medical therapy and mechanical release of adhesions in terms of final visual outcome, appearance of symblepharon and corneal vascularisation when compared in a controlled clinical setting.

Objective: To study the clinical characteristics of patients with severe ocular chemical injury in Shanghai and to determine their relationship with visual outcome., Design: Retrospective case series., Participants: A total of 79 525 in-patients at Shanghai Eye, Ear, Nose, and Throat Hospital between 1998 and 2008., Methods: Medical records of severe ocular chemical injuries were reviewed retrospectively. Patients' age, gender, occupation, location where injury occurred, the nature of chemical agent, complication, and visual acuity at final follow-up were described. The relationship between visual impairment and clinical characteristics was analyzed., Main Outcome Measures: Estimated prevalence rate, demographics of patients, nature of injury, prognosis, and factors associated with visual impairment., Results: The estimated prevalence rate in Shanghai of severe ocular chemical injury was 1.58 per 100,000. One hundred ninety cases with 239 eyes were identified for analyzing the clinical characteristics. The average age of all subjects was 35.3 ± 14.8 years with a male:female ratio of 6:1. Factory and construction worker (n = 141; 74.2% of total cases) were the most common occupations. Most of the accidents occurred at workplace (n = 144; 74.8%); the majority of injuries were caused by alkali agents (n = 129; 67.9%). Complications were found in 222 eyes (92.9%). A visual acuity of ≥ 6/60 was achieved only in 5 eyes (2.1%). In multivariate logistic regression analysis, being visually impaired was significantly associated with the patients' complication (P = 0.021)., Conclusions: The prevalence of severe ocular chemical injury in Shanghai is low. Most subjects needed surgery to restore visual function. Successful management provides a good prognosis for most patients., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction and Purpose: Various conditions may cause vascularization of the normally avascular cornea. The aim of the present study was to create a reproducible experimental model that could enable the investigation of the phenomena leading to corneal vascularization. This involved creating a software to record the experimental data, enabling a subsequent digital analysis based on the growth models. The VEGF-induced pattern of neovascularization was also investigated., Material and Methods: Twenty-seven rabbits divided in groups were used for the purposes of the present study. Some of them underwent intracorneal implants with or without vascular endothelial growth factor (VEGF) pellets, using an original microsurgical technique. Central and peripheral corneal burns were induced to other groups of animals in order to mimic the neovascularization process induced by inflammation. Finally, Dexamethasone (Maxidex) was given intraocularly, on days 1 and 3 after the onset of neovascularisation, in rabbit groups with both corneal burns and VEGF-implants. Video recording and data analysis of the corneal vascularization were made with an advanced biomicroscope, a computerized imaging system and a special software. A histochemical study of the animals' eyes was also carried out., Results and Discussion: The recorded data showed the simplicity and reproducibility of the present experimental model. The results showed the importance of VEGF as an initiator and promoter of corneal vascularization through a non-inflammatory mechanism, quite different from the inflammation illustrated by the corneal burn. At the same time, Dexamethasone therapy proved its effectiveness in corneal angiogenesis induced by thermal burn, but not by VEGF-implant.

Background: To examine the time course of hemangiogenesis, lymphangiogenesis, inflammation after corneal alkaline burns and compare with the importance of corneal hemangiogenesis, lymphangiogenesis and inflammation in allograft rejection on alkali-burned cornea bed, respectively., Methods: Rat corneal hemangiogenesis and lymphangiogenesis were examined by whole mount immunofluorescence and double enzyme-histochemistry, and the state of corneal inflammation was evaluated by inflammation index scoring and histopathology. Then, corneal transplantations were divided into six groups and performed before the burn (group A) and on day 3 (group B), 2 weeks (group C), 5 weeks (group D), 6 weeks (group E) and 8 weeks (group F) after alkaline burns, respectively. The immune rejection of grafts was evaluated by interferon-gamma, interleukin-2 enzyme-linked immunosorbent assay and slit-lamp examination., Results: Both corneal lymphatic and blood vessels reached the top 2 weeks after the burn. Corneal lymphangiogenesis disappeared 5 weeks after the burn, and corneal hemangiogenesis regressed completely 3 weeks later. Corneal inflammation was strong on day 3, but resolved 6 weeks after the burn. Compared with other groups, the mean survival time of groups B (4.67 +/- 1.03 days) and C (5.00 +/- 0.63 days) was significantly shorter (P < 0.05). The difference of mean survival time of grafts between group D (9.50 +/- 1.05 days) and group E (9.83 +/- 0.75 days), between group D and group F (10.00 +/- 0.89 days) was not significant (P > 0.05)., Conclusions: Corneal lymphangiogenesis presents for a shorter duration than corneal hemangiogenesis or corneal inflammation but plays a crucial role in allograft rejection on alkali-burned cornea bed.

Purpose: To evaluate the efficacy of amniotic membrane extract (AME) for ocular chemical burns., Methods: Prospective non-comparative interventional case series study. Consecutive 14 eyes of 11 patients with acute or chronic chemical burns, being recruited in one referral centre, received AME topically in combination with traditional treatment. Ocular discomfort, visual acuity, ocular surface inflammation, re-epithelialization, corneal thickness, corneal neovascularization and symblepharon were evaluated., Results: Symptom relieved and ocular surface inflammation reduced dramatically in all eyes. Epithelial defect healed in all eyes with acute burns, in which less than 7 clock hours of limbus was involved, after 16.6 days (1-44 days) AME treatment. AME failed to close the epithelial defect in all eyes with chronic chemical burn coexisting diffuse limbal stem cell deficiency; however, the area of epithelial defect decreased to 58% (11.1%-68.2%) at final visit. During a follow-up period of 8.2 months (6-11 months), visual acuity improved in 12 eyes (86%). There was mild neovascularization in three eyes with grade III and IV acute burns, and slow progress of neovascularization in chronic burns. Mild symblepharon developed in two eyes with grade III and IV acute burns, whereas there was no significant progress of symblepharon in chronic cases., Conclusions: Although it is a preliminary and uncontrolled study, topical application of AME is effective in reducing inflammation, promoting reepithelization in the treatment of chemical burns, especially for mild to moderate acute cases.

Purpose: To study the efficiency of the subconjunctival application of autologous regenerative factor-rich plasma (RFRP) in patients with different degrees of ocular alkali burns., Methods: Thirty-five eyes of 35 patients with ocular alkali burns were analyzed. They were classified into moderate and relevance groups according to the severity of the burn. A control group was established for each with conventional topical medical treatment; subconjunctival regenerative factor rich plasma (RFRP) was applied to the other groups. A further group was added to the severe chemical burn group, which received autohemotherapy. The clinical evolution of the lesions and the period in which the pathology prevented the patient from working were studied; monitoring was carried out until the patient had healed., Results: In the moderate chemical burns, there was a significant reduction in corneal and conjunctival epithelization times, sick leave duration, and healing time when the patients were treated with RFRP in comparison to the control group. With regard to the severe burns, significant reduction in time to corneal scarring in those treated with RFRP in comparison to traditional treatment was reported. RFRP showed, at least as effective and less side effects than the autohemotherapy., Conclusions: Subconjunctival infiltration with autologous RFRP can be considered an effective, straightforward, and economical form of treatment for burns of the ocular surface.

This study investigated the relationship between decreased outflow facility (C) and changes in hydrodynamic aqueous humor outflow patterns and morphology in cynomolgus monkey eyes with unilateral chronically elevated intraocular pressure (IOP). Argon laser photocoagulation burns to the trabecular meshwork (TM) were made in one eye of each monkey (N = 3), leaving the contralateral eye as a normotensive control. IOPs were followed by pneumatonometry for 16-70 months. C was measured by fluorophotometry before sacrifice. To label the hydrodynamic patterns of outflow, the eyes were enucleated and perfused with fluorescent microspheres (0.5 microm; 0.002%) at the last pressure measured before death minus 7 mmHg. The eyes were perfusion-fixed at the same pressure. Confocal images were taken along the inner wall (IW) of the Schlemm's canal (SC). The total length (TL) and the filtration length (FL) of the IW decorated by tracers were measured in frontal sections. The average percent effective filtration length (PEFL = FL/TL) was calculated for each eye. Sections exhibiting SC were processed and examined under light and electron microscopy. The average IOP was significantly higher in laser-treated eyes (mean +/- SD = 61.33 +/- 4.16 mmHg) than controls (22.67 +/- 4.16 mmHg, P = 0.002). The average C was 13-fold lower in laser-treated eyes (0.03 +/- 0.02 microl/min/mmHg) than controls (0.39 +/- 0.17 microl/min/mmHg, P = 0.057). By confocal microscopy, in control eyes, SC was open and a segmental distribution of microspheres was found in the TM with a greater concentration near the collector channel (CC) ostia. Much less tracer labeling was seen along SC in laser-treated eyes than control eyes. The average PEFL in controls (47.47 +/- 10.79%) was 6-fold larger than in laser-treated eyes (8.40 +/- 4.81%, P = 0.048). The average distance between the inner and outer wall of SC was 5-fold greater in control eyes (18.99 +/- 6.03 microm) than in laser-treated eyes (3.47 +/- 0.33 microm, P = 0.048). By light microscopy, there was extensive pigmentation throughout the TM, denser extracellular matrix in the JCT region, and most of SC collapsed with focal herniations of the IW and JCT protruding into the CC ostia in laser-treated eyes. By electron microscopy, few or no microspheres were observed in laser-treated areas and the areas with SC collapse. More microspheres were observed near the CC ostia area in non-lasered areas. In conclusion, in the laser-induced glaucoma model, laser damage results in a reduction in the available area for outflow across the IW of SC which contributes to the decrease in C and thus elevation of the IOP. Constriction of SC, caused by the chronic elevation of IOP, further decreases the available area for outflow across the IW which decreases C even more in a vicious cycle. This study suggests that the available area for aqueous humor outflow across the IW of SC may play a role in regulating outflow resistance and maintaining IOP.