Autologous limbal stem cell transplantation: a systematic review of clinical outcomes with different surgical techniques.

PURPOSE: To conduct a systematic review on outcomes of three different techniques of autologous limbal stem cell transplantation (LSCT): conjunctival-limbal autografting (CLAu), cultivated limbal epithelial transplantation (CLET) and simple limbal epithelial transplantation (SLET), in unilateral limbal stem cell deficiency (LSCD). METHODS: Literature searches were conducted in MEDLINE (Ovid), Embase, Web of Science and Cochrane Central Register. Standard systematic review methodology was followed using Meta-analysis of Observational Studies in Epidemiology guidelines. Studies with a sample size of more than 10 eyes were included. The primary outcome measure of efficacy was restoration of a completely epithelised, stable and avascular corneal surface (anatomical success). The secondary outcome measure of efficacy was improvement in best-corrected visual acuity of two-lines or greater (functional success). RESULTS: The review identified 22 non-comparative case series, which included 1023 eyes. Ocular burns were the major (88%) indication for surgery. Overall, at a median postoperative follow-up of 1.75 years, autologous LSCT for unilateral LSCD showed anatomical and functional success rates of 69% and 60%, respectively, without any serious adverse events in the donor eye. The follow-up duration and indications for surgery were comparable across all groups (p>0.05). The anatomical and functional success rates of SLET (78%; 68.6%) and CLAu (81%; 74.4%) were comparable, and significantly better than those of CLET (61.4%; 53%; p=0.0048). CONCLUSION: Autologous LSCT is a safe and effective treatment for unilateral LSCD. In the absence of randomised controlled trials, existing evidence clearly suggests that clinical outcomes are better with SLET and CLAu as compared with CLET.

Corneal Laceration Associated With Upper Eyelid Blepharoplasty.

A 64-year-old woman underwent bilateral upper eyelid blepharoplasty and subsequently presented with decreased vision at her first postoperative visit 1 week later. She was found to have an 8-mm partial-thickness corneal laceration of her left eye and underwent immediate surgical laceration repair. The laceration etiology was thought to be related to damage from the initial blepharoplasty incision or Bovie cautery tip-induced laceration. After laceration repair, she had residual astigmatism and corneal scarring leading to poor vision. Corneal injuries, including abrasions and perforations, are rare complications of blepharoplasty, and the case in this study is the first report of corneal laceration following blepharoplasty. Corneal perforations and lacerations can lead to significant damage and vision loss, indicating a need for careful attention to surgical technique and instrument placement intraoperatively, routine use of corneal protectors even during superficial aesthetic procedures such as blepharoplasties, and comprehensive postoperative patient instructions.A 64-year-old woman who underwent an upper eyelid blepharoplasty sustained a partial-thickness corneal laceration of her OS, which required emergent repair and resulted in persistent vision loss secondary to large corneal scar.

Rose Bengal Photodynamic Antimicrobial Therapy for Patients With Progressive Infectious Keratitis: A Pilot Clinical Study.

PURPOSE: To report clinical outcomes of rose bengal photodynamic antimicrobial therapy (RB-PDAT) as an adjunct treatment for severe, progressive infectious keratitis. DESIGN: Consecutive interventional case series. METHODS: Patients with progressive infectious keratitis unresponsive to standard medical therapy underwent RB-PDAT at the Bascom Palmer Eye Institute from January 2016 through March 2018. RB-PDAT was performed by applying a solution of rose bengal (0.1% or 0.2% RB in balanced salt solution) to the de-epithelialized cornea for 30 minutes, followed by irradiation with a 6 mW/cm2 custom-made green LED source for 15 minutes (5.4 J/cm2). RESULTS: The current study included 18 patients (7 male and 11 female) ranging from 17 to 83 years old. Acanthamoeba was the most frequent microbe (10/17; 59%), followed by Fusarium spp. (4/17; 24%), Pseudomonas aeruginosa (2/17; 12%), and Curvularia spp. (1/17; 6%); 1 patient had no confirmed microbiologic diagnosis. Main clinical risk factor for keratitis included contact lens wear (79%). The average area of epithelial defect prior to first RB-PDAT was 32 ± 27 mm2 and average stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 269 ± 75 µm. Successful RB-PDAT (avoidance of therapeutic keratoplasty) was achieved in 72% of the cases, with an average time to clinical resolution (decreased pain and inflammation with re-epithelialization and infiltrate resolution) of 46.9 ± 26.4 days after RB-PDAT. Time of follow-up after RB-PDAT was 13.3 ± 5.7 months. CONCLUSION: RB-PDAT can be considered as an adjunct therapy for cases of severe, progressive infectious keratitis before performing a therapeutic keratoplasty.

Fibroblast growth factor receptor 1 (FGFR1) as a therapeutic target in adenoid cystic carcinoma of the lacrimal gland.

Identification of molecular targets is the first step in developing efficacious therapeutic strategies for tumors. A tumors' biological response to perturbagens yields important information on the molecular determinants for tumor growth. The aim of this study was to characterize the response of adenoid cystic carcinoma of the lacrimal gland (LGACC) to intra-arterial cytoreductive chemotherapy (IACC) in order to identify novel targets to enhance therapy. We performed high-throughput proteomic analysis on paired samples from pre-IACC diagnostic biopsies and post-IACC excised tumor samples from 6 LGACC patients. This proteomic analysis provides a comprehensive landscape of the cellular compartments contained within the excised tumors. Interestingly, we found a strong upregulation across the fibroblast growth factor (FGF) signaling pathway, with FGF receptor 1 (FGFR1) exhibiting a consistent and significant upregulation in all post-IACC samples. We thus evaluated the therapeutic efficacy of a novel FGFR1 selective inhibitor, AZD4547, in combination with cisplatin on LGACC cells in-vitro. The combination index (CI) value (<0.895) demonstrated synergistic effect of AZD4547 and cisplatin in inhibiting cell growth and viability (p<0.02), with a differential response seen in post-IACC cultures when compared to pre-IACC cultures. The combination approach showed synergy of the drugs in the migration assay. Western blot analysis indicated a significant upregulation of cleaved caspase-3 and downregulation the expression of FGFR1 (p<0.05) with the combination treatment as compared to either agent independently. Our findings demonstrate that FGFR1 inhibition potentiates the cytoreductive effects of cisplatin and suggest a potential therapeutic benefit of using AZD4547 in the management of LGACC.

Limbal ischemia: Reliability of clinical assessment and implications in the management of ocular burns.

PURPOSE: Limbal ischemia is an important prognostic factor in the management of ocular burns. In this study, we evaluated the reliability of clinically assessing limbal ischemia among ophthalmic professionals. METHODS: This study included 111 ophthalmic professionals who were shown 12 diffuse illumination color slit-lamp photographs of eyes with recent chemical injuries. Respondents were asked whether the photos were assessable and if yes, then to indicate the presence, location, and grade of limbal ischemia in each case. The responses were collected using a standard data collection sheet and the inter-observer agreement was calculated. RESULTS: All participants responded to every question. Of the 1,332 responses, images were deemed assessable in 1,222 (91.7%) instances. The overall agreement (Fleiss' kappa) for the presence of limbal ischemia and severity of limbal ischemia was 0.106 and 0.139, respectively (P < 0.012). Among the four groups of observers, practicing cornea specialists displayed significantly (P < 0.003) higher kappa values (0.201-0.203) when compared to residents (0.131-0.185), fellows (0.086-0.127), and optometrists (0.077-0.102). All indicated a poor level of inter-rater consistency. CONCLUSION: The results indicate that clinical assessment of limbal ischemia is highly subjective and there is lack of reliability even among cornea specialists who regularly manage patients with ocular burns. A non-invasive, standardized, objective, accurate, and reliable modality for ocular surface angiography is desperately needed for proper assessment and prognostication of ocular burns.

Ablative Fractional Laser Resurfacing With Laser-Assisted Delivery of 5-Fluorouracil for the Treatment of Cicatricial Ectropion and Periocular Scarring.

PURPOSE: Cicatricial ectropion and periocular scarring can cause significant functional and cosmetic deficits. Surgical treatments can be associated with recicatrization, donor site morbidity, and textural and pigmentary abnormalities. This case series reports on efficacy and safety of a novel nonsurgical approach to treating cicatricial ectropion using ablative fractional laser resurfacing and laser-assisted delivery of 5-fluorouracil. METHODS: A retrospective review was conducted of all patients at a single institution who received ≥3 rounds of ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil. Six patients with cicatricial ectropion and periocular scarring secondary to reconstructive surgery, traumatic lacerations, and facial burns were included. Aesthetic and functional improvement were evaluated via fluorescein staining, tear breakup time, external photography, questionnaires gauging dry eye symptoms, and scar appearance. RESULTS: All patients showed functional improvement based on fluorescein staining (mean improvement 6.0 ± 1.4; p = 0.0007) and other indicators of dry eye. All 4 patients with lagophthalmos improved and 2 showed complete resolution. All patients demonstrated significant cosmetic improvement based on a validated scar assessment questionnaire (mean improvement 37.5 ± 18.9; p = 0.004), and 5 of 6 patients reported improved satisfaction with scar appearance (mean improvement 19.3 ± 12.8; p = 0.014). There were no adverse effects reported. CONCLUSIONS: Ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil appears to be a safe and effective modality for treating the functional and aesthetic abnormalities associated with periocular scarring, yielding results that are difficult to attain through surgery alone. Optimal management of cicatricial ectropion and periocular scarring often requires multimodality treatment, and ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil may be considered as part of a comprehensive approach to managing periocular scars.

Rose Bengal Photodynamic Antimicrobial Therapy: A Novel Treatment for Resistant Fusarium Keratitis.

PURPOSE: To evaluate the efficacy of rose bengal PDAT for the management of a patient with multidrug-resistant Fusarium keratoplasticum keratitis unresponsive to standard clinical treatment. METHODS: This case report presents a clinical case of F. keratoplasticum keratitis not responsive to standard medical care. In vitro studies from patients culture isolated responded to rose bengal PDAT. Patient received two treatments with rose bengal 0.1% and exposure to green light with a total energy of 2.7 J/cm. RESULTS: In vitro results demonstrated the efficacy of rose bengal PDAT a multidrug-resistant F. keratoplasticum species. There was complete fungal inhibition in our irradiation zone on the agar plates. In the clinical case, the patient was successfully treated with 2 sessions of rose bengal PDAT, and at 8-month follow-up, there was neither recurrence of infection nor adverse effects to report. CONCLUSIONS: Rose bengal PDAT is a novel treatment that may be considered in cases of aggressive infectious keratitis. Further studies are needed to understand the mechanisms of PDAT in vivo.

Modified simple limbal epithelial transplantation using cryopreserved amniotic membrane for unilateral limbal stem cell deficiency.

PURPOSE: To report the results of simple limbal epithelial transplantation using a double-layered cryopreserved amniotic membrane graft for the management of unilateral limbal stem cell deficiency. DESIGN: Retrospective case series. METHODS: Four consecutive patients with unilateral partial (2 eyes) and total (2 eyes) limbal stem cell deficiency secondary to ocular surface burns (2 eyes), trauma (1 eye) and conjunctival melanoma treatment (1 eye) underwent modified simple limbal epithelial transplantation at Bascom Palmer Eye Institute. Preoperative and postoperative visual acuity and quality of corneal epithelium were evaluated. RESULTS: The patients were followed up for a mean ± standard deviation of 7.5 ± 1.3 months. The donor eye returned to a healthy state in all patients. All patients had significant improvement in visual acuity and resolution of ocular pain in the affected eye. Regular corneal epithelium and a quiet ocular surface were obtained in all patients by a median of 4 weeks. CONCLUSIONS: Compared with the currently used surgical techniques for management of limbal stem cell deficiency, simple limbal epithelial transplantation seems to be a safe, reproducible, and effective alternative. The use of a double layer allows more protection for the explant without impacting outcomes. Also, the use of cryopreserved amniotic membrane allows surgeons to perform this procedure in the Unites States. More cases with longer follow-up will be needed to assess the outcomes further.

Rapid capsular phimosis in retinitis pigmentosa.

This case report retrospectively reviews the outcome of a 43-year-old man with retinitis pigmentosa who suffered rapid anterior capsular phimosis in each eye within 3 weeks following uncomplicated phacoemulsification with continuous curvilinear capsulorrhexis and single-piece acrylic intraocular lens (IOL) implantation. Anterior YAG capsulotomy was successfully performed in both eyes. It has been previously documented in the literature that capsular phimosis is more common in patients with retinitis pigmentosa. However, in the cases that were reviewed, capsular contracture progressed much less rapidly than in this patient. It is proposed that zonular dehiscence or increased lens epithelial cell fibrosis accompanying retinitis pigmentosa may be responsible for phimosis following phacoemulsification; in this case, the single-piece IOL may have offered less resistance to capsular contraction. Using a three-piece IOL, capsular tension ring, or making radial relaxing incisions in the anterior lens capsule may be useful approaches to minimize the aforementioned complications in patients with retinitis pigmentosa and cataracts.