Modified Limbal-Conjunctival Autograft Surgical Technique: Long-Term Results of Recurrence and Complications.

PURPOSE: The aim of this study was to report the recurrence and complication rates of a modified limbal-conjunctival autograft surgical technique for pterygium excision. METHODS: This was a retrospective, single-surgeon, single-operating environment, consecutive case series of 176 eyes in 163 patients with a biopsy-proven diagnosis of pterygium. All patients underwent excision using a 23-gauge needle to "behead" the pterygium head, followed by a limbal-conjunctival autograft including ∼50% of the palisades of Vogt. Outcomes measured included recurrence, defined as any conjunctival fibrovascular growth, and complication rates. Correlations between preoperative patient characteristics, pterygium morphology, and intraoperative factors (width of corneal extension, conjunctival defect, and graft) with postoperative recurrence were examined using logistic regression models. RESULTS: The median age was 59.5 years and 122 eyes (69.3%) had primary pterygium (type I: 17%, II: 37.5%, and III: 45.5%). Kaplan-Meier analysis demonstrated the median pterygium-free follow-up period to be 723 days (range 46-7230 days). Recurrence was observed in 3 eyes of 2 patients (1.7%). No postoperative graft-related complications were observed. Postoperative symptomatology was transient. Age demonstrated a negative correlation with recurrence (odds ratio 0.888, 95% CI, 0.789-0.998, P = 0.046). However, no other correlations with preoperative or intraoperative factors, including whether pterygium was primary or recurrent, were identified (all P > 0.05). CONCLUSIONS: This modified limbal-conjunctival autograft technique represents an effective alternative that offers a very low recurrence rate and avoids extensive dissection or antimetabolites, with minimal complications and transient postoperative symptomatology, over a long-term follow-up period. This technique is relatively simple and successful for both primary and recurrent pterygia. Future comparative studies with other surgical techniques may determine which are superior.

Handing it to pterygium: Explaining pterygium laterality.

PURPOSE: To evaluate any correlation between pterygium laterality and patient handedness. METHODS: Our study represents a retrospective observational study of a series of consecutive pterygium patients recruited from two centres. Each patient was assessed for their handedness which was compared to the laterality of their presenting pterygium. Patients that possessed bilateral disease comparisons between pterygium size and handedness were made. Correlation statistics were performed to compare patient handedness and pterygium location (right or left). For patients possessing bilateral disease only, the pre-surgical differences between lengths and areas of pterygium were calculated and compared. RESULTS: A total of 219 patients were recruited into our study. 172 patients possessed unilateral disease and in 47 patients, the disease was bilateral. A significant association was identified between handedness and pterygium laterality (p < 0.001). Patients with right-sided pterygia were more likely to be right-handed (OR 2.327) and left-sided presentations who were more likely to be left-handed (OR 5.717). For bilateral presentations, patients were found to have longer (mean increase 3.50 ± 0.47 mm) and larger (mean increase 4.38 ± 0.48 mm2) pterygia in the eye ipsilateral to their dominant hand. CONCLUSIONS: A new insight of handedness as a contributing factor to pterygium laterality is consistent with evidence relating to the asymmetrical development of cortical cataract as well as to theories underlying the geometry of ocular UV exposure. A more complete understanding of factors contributing to ocular insolation may further inform as to improved protective measures and provides further evidence for the role of peripheral light focusing in pterygium pathogenesis.

The treatment of recurrent conjunctival and corneal intraepithelial neoplasia with interferon alfa-2b and retinoic acid: ~9 years' follow-up on tumor control.

PURPOSE: To evaluate the long-term follow-up of recurrent conjunctival and corneal intraepithelial neoplasia (CCIN) treated with combination topical interferon alfa-2b and retinoic acid (I/RA). METHODS: Our study represents a retrospective observational interventional series of 82 eyes from 82 patients from a single institution, reviewed for CCIN. All were administered topical interferon alfa-2b 1 million IU/mL QID and retinoic acid 0.01% every other day. Patients had been diagnosed by biopsy. A Kaplan-Meier survival analysis, Wilcoxon signed-rank test and a multivariate logistic regression were statistical tests used to correlate recurrence with patient and tumor variables. RESULTS: 79 eyes assessed for CCIN diagnoses and treated with I/RA achieved tumor resolution. The median tumor-free follow-up was ~109.1 months with a median time to resolution being ~2.8 months. Our median treatment duration was ~11.3 months. The greatest difference in the mean total residual tumor size was identified between Months 0-1 [-7.63 mm2]. The difference in mean total residual tumor size remained significant till 36-months. A statistically significant correlation with recurrence was identified for biopsy type [OR 0.138]. 6 patients experienced papillary conjunctivitis which resolved with dosage reduction. CONCLUSIONS: Combination I/RA was effective in treating CCIN lesions with few transient side effects. The combination of retinoids and interferons may represent a viable topical therapeutic agent with an extended tumor-free follow-up and a large proportion of our study's patients achieving >10 year's tumor-free follow-up. Our treatment duration is long, but by cost-comparing surgical against medical interventions, topical I/RA may serve as a safe and effective alternative.

Expert-led didactic versus self-directed audiovisual training of confocal laser endomicroscopy in evaluation of mucosal barrier defects.

BACKGROUND AND STUDY AIMS: Confocal laser endomicroscopy (CLE) allows mucosal barrier defects along the intestinal epithelium to be visualized in vivo during endoscopy. Training in CLE interpretation can be achieved didactically or through self-directed learning. This study aimed to compare the effectiveness of expert-led didactic with self-directed audiovisual teaching for training inexperienced analysts on how to recognize mucosal barrier defects on endoscope-based CLE (eCLE). MATERIALS AND METHODS: This randomized controlled study involved trainee analysts who were taught how to recognize mucosal barrier defects on eCLE either didactically or through an audiovisual clip. After being trained, they evaluated 6 sets of 30 images. Image evaluation required the trainees to determine whether specific features of barrier dysfunction were present or not. Trainees in the didactic group engaged in peer discussion and received feedback after each set while this did not happen in the self-directed group. Accuracy, sensitivity, and specificity of both groups were compared. RESULTS: Trainees in the didactic group achieved a higher overall accuracy (87.5 % vs 85.0 %, P  = 0.002) and sensitivity (84.5 % vs 80.4 %, P  = 0.002) compared to trainees in the self-directed group. Interobserver agreement was higher in the didactic group (k = 0.686, 95 % CI 0.680 - 0.691, P  < 0.001) than in the self-directed group (k = 0.566, 95 % CI 0.559 - 0.573, P  < 0.001). Confidence (OR 6.48, 95 % CI 5.35 - 7.84, P  < 0.001) and good image quality (OR 2.58, 95 % CI 2.17 - 2.82, P  < 0.001) were positive predictors of accuracy. CONCLUSION: Expert-led didactic training is more effective than self-directed audiovisual training for teaching inexperienced analysts how to recognize mucosal barrier defects on eCLE.

Conjunctival Squamous Cell Carcinoma with Corneal Stromal Invasion in Presumed Pterygia: A Case Series.

AIM: To describe 4 cases of conjunctival squamous cell carcinoma (SCC) with corneal stromal invasion. METHODS: Retrospective, clinicopathologic case series. RESULTS: All patients had prior resections of presumed pterygia. The degree of corneal involvement dictated the extent of surgical management. One eye with localized invasion was treated with lamellar keratoplasty and plaque brachytherapy. Another case with widespread invasion warranted penetrating keratoplasty and eventual enucleation. Two cases were treated medically prior to surgical intervention: one with localized invasion was treated with topical interferon and retinoic acid; another with significant inflammation was treated with doxycycline and fluorometholone. The patient who underwent keratoplasty and brachytherapy had no recurrence after 7 years of follow-up. Those initially treated medically had resections of recurrence but ultimately required enucleation. Histologically, specimens demonstrated SCC invading the deep corneal stroma, with 2 tumors of the mucoepidermoid type. CONCLUSIONS: This series demonstrates the importance of maintaining clinical suspicion of conjunctival squamous neoplasia in pterygia. We recommend that all excised pterygia be submitted for histopathologic evaluation and be carefully evaluated for dysplasia and variants of SCC associated with increased risk of intraocular invasion. Undetected ocular surface squamous neoplasia may give rise to potentially vision- and eye-threatening invasive corneal SCC.

Impaired Intestinal Permeability Contributes to Ongoing Bowel Symptoms in Patients With Inflammatory Bowel Disease and Mucosal Healing.

BACKGROUND & AIMS: Many patients with inflammatory bowel diseases (IBD) have ongoing bowel symptoms of diarrhea or abdominal pain despite mucosal healing. We investigated whether impaired intestinal permeability contributes to these symptoms. METHODS: We performed a prospective study of intestinal permeability, measured by endoscopic confocal laser endomicroscopy in 110 consecutive subjects (31 with ulcerative colitis [UC], 57 with Crohn's disease [CD], and 22 healthy individuals [controls]) in Sydney, Australia from May 2009 and September 2015. Symptomatic CD was defined by a CD Activity Index score of 150 or more and symptomatic UC by a partial Mayo score of 2 or more. Mucosal healing was defined as CD Endoscopic Index of Severity of 0 in CD or Mayo endoscopic sub-score of 0-1 for patients with UC. Intestinal permeability was quantified by the Confocal Leak Score (CLS; range: 0=no impaired permeability to 100=complete loss of barrier function). The primary endpoint was intestinal permeability in patients with symptomatic IBD in mucosal healing vs patients with asymptomatic IBD in mucosal healing. We determined the sensitivity and specificity of CLS in determining symptoms based on receiver operating characteristic analysis. RESULTS: Ongoing bowel symptoms were present in 16.3% of patients with IBD and mucosal healing (15.4% of patients with CD, 17.4% with UC). Patients with symptomatic IBD had a significantly higher median CLS (19.0) than patients with asymptomatic IBD (7.3; P < .001) or controls (5.9, P < .001). There were no significant differences between patients with IBD in remission vs controls (P = .261). Median CLS was significantly higher in patients with symptomatic than asymptomatic CD (17.7 vs 8.1; P = .009) and patients with symptomatic than asymptomatic UC (22.2 vs 6.9; P = .021). A CLS of 13.1 or more identified ongoing bowel symptoms in patients with IBD and mucosal healing with 95.2% sensitivity and 97.6% specificity; the receiver operating characteristic area under curve value was 0.88. Based on this cutoff, 36.2% of patients with IBD in mucosal healing have increased intestinal permeability. On regression analysis, every increase in CLS of 1.9 correlated with an additional diarrheal motion per day (P = .008). CONCLUSIONS: In a prospective study of intestinal permeability in patients with IBD and mucosal healing, we associated impaired intestinal permeability with ongoing bowel symptoms; increases in permeability correlated with increased severity of diarrhea. Resolution of mucosal permeability beyond mucosal healing might improve outcomes of patients with IDB (ANZCTR.org.au: ACTRN12613001248752).

The learning curve, interobserver, and intraobserver agreement of endoscopic confocal laser endomicroscopy in the assessment of mucosal barrier defects.

BACKGROUND AND AIMS: Confocal laser endomicroscopy can dynamically assess intestinal mucosal barrier defects and increased intestinal permeability (IP). These are functional features that do not have corresponding appearance on histopathology. As such, previous pathology training may not be beneficial in learning these dynamic features. This study aims to evaluate the diagnostic accuracy, learning curve, inter- and intraobserver agreement for identifying features of increased IP in experienced and inexperienced analysts and pathologists. METHODS: A total of 180 endoscopic confocal laser endomicroscopy (Pentax EC-3870FK; Pentax, Tokyo, Japan) images of the terminal ileum, subdivided into 6 sets of 30 were evaluated by 6 experienced analysts, 13 inexperienced analysts, and 2 pathologists, after a 30-minute teaching session. Cell-junction enhancement, fluorescein leak, and cell dropout were used to represent increased IP and were either present or absent in each image. For each image, the diagnostic accuracy, confidence, and quality were assessed. RESULTS: Diagnostic accuracy was significantly higher for experienced analysts compared with inexperienced analysts from the first set (96.7% vs 83.1%, P < .001) to the third set (95% vs 89.7, P = .127). No differences in accuracy were noted between inexperienced analysts and pathologists. Confidence (odds ratio, 8.71; 95% confidence interval, 5.58-13.57) and good image quality (odds ratio, 1.58; 95% confidence interval, 1.22-2.03) were associated with improved interpretation. Interobserver agreement κ values were high and improved with experience (experienced analysts, 0.83; inexperienced analysts, 0.73; and pathologists, 0.62). Intraobserver agreement was >0.86 for experienced observers. CONCLUSION: Features representative of increased IP can be rapidly learned with high inter- and intraobserver agreement. Confidence and image quality were significant predictors of accurate interpretation. Previous pathology training did not have an effect on learning.

Significance of Fuchs Flecks in Patients With Pterygium/Pinguecula: Earliest Indicator of Ultraviolet Light Damage.

PURPOSE: Fuchs flecks (FFs) have been previously identified at the leading edge of pterygia and may represent collections of epithelial stem-like cells that give rise to this condition. This study aims to evaluate the clinical significance of FFs in patients with ocular surface disorders, such as pterygium and pinguecula, by in vivo confocal microscopy (IVCM). METHODS: This study is a Single-center, retrospective, observational case series of 40 eyes from 20 patients with clinical diagnoses of pinguecula or pterygium, or both. IVCM (Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany) was performed on patients with pinguecula or pterygium, or both. The presence of FFs on the ocular surface of patients with pterygium and pinguecula was assessed by IVCM and subsequently documented. RESULTS: FFs were present in 24 of 30 eyes (80.0%) in paired macroscopically normal nasal or limbal regions, 19 of 20 (95.0%) in pinguecula, 13 of 15 (86.7%) in primary pterygia, and 7 of 7 (100%) in recurrent pterygia. CONCLUSIONS: High rates of FFs were identified at the head of pinguecula, primary pterygium, recurrent pterygium, and macroscopically normal nasal and temporal limbus. We postulate that FFs may represent precursor lesions to UV-associated ocular surface pathology. Identification of Fuchs fleck by IVCM may permit clinicians to predict the patients who may progress to develop more advanced pathology.