The utility of anterior segment optical coherence tomography angiography for the assessment of limbal stem cell deficiency

PurposeTo determine the utility of anterior segment optical coherence tomography angiography (AS-OCTA) in assessing limbal stem cell deficiency (LSCD).MethodsTwenty-six eyes of 24 LSCD patients, classified clinically into stage I, II and III, and 12 eyes of 12 healthy subjects were included. AS-OCTA images were analyzed by two masked observers, measuring the maximum corneal vascular extension (CoVE) from the limbus to the furthest vessel over the cornea, and corneal vascular thickness (CoVT) from the most superficial to the deepest corneal vessel.ResultsCoVE was 0.27 ± 0.10, 0.79 ± 0.21, 1.68 ± 0.89 and 2.53 ± 0.82 mm in controls, stage I, II and III LSCD, respectively (p < 0.001). The CoVT was 51.0 ± 19.4, 113.7 ± 36.6, 129.7 ± 39.3 and 336.0 ± 85.0 μm, respectively (p < 0.001). There was a significant difference in CoVE and CoVT between all stages compared to controls, and between stage I and III LSCD (p < 0.001). Further, CoVE showed a significant difference between stage I and II, whereas CoVT showed a significant difference between stage II and III LSCD (p < 0.001). BCVA showed strong correlation with CoVT (r = 0.765, p < 0.001) and moderate correlation with CoVE (r = 0.547, p = 0.001). AS-OCTA parameters showed excellent intra- and inter-class correlation coefficients (>0.900).ConclusionLSCD demonstrates significant changes in CoVE and CoVT as early as stage I LSCD in comparison to controls. CoVE and CoVT strongly correlate to both disease severity and BCVA. AS-OCTA may provide novel quantitative and non-invasive parameters to assess LSCD.     

A reliable animal model of corneal stromal opacity: Development and validation using in vivo imaging

PurposeTo validate an animal model of corneal stromal opacity by using objective vision-independent in vivo imaging metrics.MethodsThis was a prospective study, with two arms: (i) observational human arm which included 14 patients with healed unilateral ulcerative keratitis; and (ii) experimental rabbit arm, which included 6 New Zealand white rabbits. A 3-mm central wound was created in the left eye of the rabbits by manually removing 200–250 μm of the superficial stroma, followed by rotating-burr application. Both groups underwent photography, high-resolution anterior segment optical coherence tomography, and Scheimpflug imaging using similar diagnostic platforms and standardized image capturing protocols. Parameters studied were relative change in (i) corneal thickness; (ii) corneal epithelial: stromal (E:S) reflectivity ratio; (iii) corneal stromal light scattering using densitometry; and (iv) central corneal keratometry.ResultsIn the experimental arm, there was a significant decrease in corneal thickness (273 ± 51.3 vs. 407.3 ± 10.3 μm, p = 0.0038), E:S reflectivity ratio (0.71 ± 0.09 vs. 0.99 ± 0.06, p = 0.0018), and keratometry (40.4 ± 2.3 vs. 45.8 ± 0.9D, p = 0.0033) and increase in densitometry (54.2 ± 11.65 vs.18.7 ± 3.8 GSU, p = 0.0001) from baseline, which stabilized at 4 to 8-weeks post-wounding (p > 0.3632). At 8-weeks, the relative change from baseline in corneal thickness (28.4 ± 13.5% vs.22.4 ± 13%, p = 0.368), E:S reflectivity ratio (28.1 ± 11.5% vs. 30.6 ± 8.9%, p = 0.603), corneal densitometry (204.17 ± 97.3% vs. 304.9 ± 113.6%, p = 0.1113), and central corneal keratometry (13.6 ± 6.9% vs. 18.9 ± 7.4%, p = 0.1738) in rabbits was similar to human corneal scars.ConclusionThe animal model of corneal opacification was objectively comparable to human post-keratitis scars and can be valuable for in vivo evaluation of emerging therapies for corneal opacities.     

Infrared meibography allows detection of dimensional changes in meibomian glands following intranasal neurostimulation

PurposePatients with dry eye disease (DED) may suffer from decreased tear break-up time due to meibomian gland (MG) dysfunction. Infrared meibography (IR Meibography) uses infrared wavelength light to visualize meibomian glands in vivo. We aimed to explore the feasibility of using serial IR Meibography imaging to assess morphological changes in MGs as an indirect measure of functionality, following intranasal neurostimulation (ITN).MethodsFifteen DED subjects were prospectively enrolled in a single-center, single-arm study. Changes in MGs were captured using IR meibography (RTVUE-XR, Optovue, Inc. Fremont, CA, USA) on the lower eyelids before and after 3 min of ITN (TrueTear®, Allergan, Dublin, Ireland) use that delivers a microcurrent to sensory neurons of the nasal cavity. The same MGs were selected pre- and post-stimulation, and MG area and perimeter were analyzed by two masked observers.ResultsMean (±SD) pre- and post-stimulation MG areas were 2,187.60 ± 635.88 μm² and 1,933.20 ± 538.55 μm², respectively. The mean change in area, 254.49 μm², representing an 11.6% reduction following ITN use, was statistically significant (p = 0.001). Mean (±SD) pre- and post-stimulation MG perimeters were 235.9 ± 51.38 μm and 222.2 ± 47.72 μm, respectively. The mean change in perimeter, 13.7 μm, representing a 5.81% reduction following ITN use, was statistically significant (p = 0.012).ConclusionsOur study shows that IR meibography can be used to detect immediate changes in gland area and perimeter, an indirect measure of MG activity following intervention by ITN.     

Anterior-segment spectral domain optical coherence tomography in epidermolysis bullosa

PurposeAssess epidermolysis bullosa (EB)-related corneal pathology using anterior segment optical coherence tomography (AS-OCT) and correlate imaging with clinical metrics in EB patients versus age-matched controls.MethodsEB patients and controls were recruited during an EB conference (July 2018) and at Tufts Medical Center (June–August 2019). Subjects completed a questionnaire, had best corrected visual acuity (BCVA) tested, and underwent AS-OCT scanning. Stromal and epithelial thickness were measured. Depth, length, and type of the three largest lesions were assessed by a masked examiner using a novel pathology grading system. Multivariate analysis of AS-OCT findings and clinical metrics was performed.Results62 EB patients and 60 age-matched controls were enrolled. Mean BCVA was 1.8 lines worse in patients (p < 0.001). Vision loss was associated with increased stromal thickness. Discrete lesions were seen in 60.2% of patient eyes, averaging 1.71 ± 1.75 lesions in patients and 0.14 ± 0.42 in controls (p < 0.001). Mean primary lesion depth was 151.88 ± 97.49 μm in patients. Patients showed significant stromal thickening versus controls and lesions were most common in the periphery and inferiorly. Differences in frequency and duration of abrasions and severity of pain were all statistically and clinically significant in patients versus controls (p < 0.001).ConclusionsAS-OCT can visualize and quantify differences in the corneas of EB patients compared with age-matched controls. Novel findings include quantification of average depth, length, and severity of discrete lesions, and sparing of the superior quadrant from stromal thickening in EB patients. These results support use of AS-OCT and a questionnaire in clinical trials for new EB therapies.     

Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study

PurposeTo evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls.MethodsIn this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10 s were classified as DED. Those with an anesthetized Schirmer's strip of less than 5 mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers.ResultsCompared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0 ± 687.7 μm/mm² vs. 21,014.7 ± 706.5, p = 0.026) and main (7,718.9 ± 273.9 vs. 9,561.4 ± 369.8, p < 0.001) nerve density, as well as lower total (15.5 ± 0.7/frame vs. 20.5 ± 1.3, p = 0.001), main (3.0 ± 0.1 vs. 3.8 ± 0.2, p = 0.001) and branch (12.5 ± 0.7 vs. 16.5 ± 1.2, p = 0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9 ± 830.7 vs. 15,942.2 ± 1,135.7, p = 0.006), branch nerve density (11,964.9 ± 749.8 vs. 8,765.9 ± 798.5, p = 0.006), total nerves number (16.9 ± 0.8/frame vs. 13.0 ± 1.2, p = 0.002), and branch nerve number (13.8 ± 0.8 vs. 10.2 ± 1.1, p = 0.002).ConclusionsPatients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.     

Optical coherence tomography angiography in the evaluation of vascular patterns of ocular surface squamous neoplasia during topical medical treatment

PurposeOptical coherence tomography angiography (OCTA) was utilized to examine changes in ocular surface squamous neoplasia (OSSN) vascular patterns over time in individuals treated with topical medical therapy.MethodsTen individuals with OSSN diagnosed by clinical examination and high resolution (HR)-optical coherence tomography (OCT) were recruited. All individuals received topical immuno- or chemotherapy. OCTA images were obtained and analyzed at three points: presentation, mid-treatment and tumor resolution. Tumor metrics including tumor area (TA), tumor volume (TV), tumor depth (TD), and total tumor density (TTD) were calculated. Vessel area density (VAD) was also quantified within the OSSN, the subepithelium under and adjacent to the OSSN and the subepithelium of the uninvolved, contralateral eye. Vascular network changes were also subjectively evaluated.ResultsTA, TV, TD and TTD all significantly decreased with time (p < 0.001). The mean VAD within the OSSN significantly decreased (p < 0.001) between visits (presentation: 26.52 ± 6.8%, mid-treatment: 7.19 ± 5.88%, tumor resolution: 0.11 ± 0.34%). The mean subepithelial VAD under the OSSN also decreased with time (23.22 ± 11.03%, 20.99 ± 5.99% and 19.58 ± 7.08%), and after resolution the sub-tumor VAD (19.58 ± 7.08%) was comparable to the subepithelial VAD in the contralateral eye (15.47 ± 4.37%, p > 0.05). The mean VAD in the subepithelium adjacent to the OSSN increased with treatment, then decreased significantly between mid-treatment and resolution (23.26 ± 4.54, 28.30 ± 7.43% and 21.68 ± 6.10%, p = 0.009). Qualitatively, the tumor subepithelial vascular network was complex and dense but with tumor resolution appeared less tortuous and similar to the uninvolved eye.ConclusionOCTA provided insight into the pathophysiology of tumor angiogenesis, showing decreased vascular density and normalization of vascular networks associated with tumor resolution.     

Comparison of clinical characteristics of post-refractive surgery-related and post-herpetic neuropathic corneal pain

PurposeTo compare the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP) to controls.MethodsSixteen patients with RS-NCP and 7 patients with H-NCP, and 37 healthy reference age- and sex-matched healthy controls were included to the study. The medical records were reviewed for demographic features, detailed disease history, ocular surface disease index (OSDI), ocular pain assessment survey (OPAS) scores. IVCM images of patients were analyzed and compared to reference controls by two masked observers.ResultsThe mean pain intensity score for the last 24 h (5.1 ± 2.4 vs. 3.9 ± 1.2; p = 0.27), last 2 weeks (6.1 ± 2.5 vs. 4.8 ± 2.3; p = 0.13) for RS-NCP vs. H-NCP respectively, and quality of life scores (p = 0.23) were similar in both groups. Quality of life, especially mood (p = 0.06) and enjoying life/relations to others (p = 0.10) were affected in both groups, but were not statistically significant between groups. The mean total nerve density was lower in RS-NCP (5,702.4 ± 4,599.0 μm/mm²) compared to their respective controls (26,422.8 ± 4,491.0; p < 0.001) and in the H-NCP group (2,149.5 ± 2,985.9) compared to their respective controls (22,948.8 ± 3,169.0; p < 0.001). Alterations in DC density were similar between all groups (38.3 ± 48.0 cells/mm² in RS-NCP, 61.0 ± 76.9 in H-NCP, p = 0.95).ConclusionNeuropathic corneal pain patients due to refractive surgery show similar clinical characteristics, pain levels, quality of life impact, and IVCM findings as patients with NCP due to herpetic eye disease.     

Effects of meibomian gland dysfunction and aqueous deficiency on friction-related disease

PurposeTo evaluate the effects of meibomian gland dysfunction (MGD) and aqueous deficiency (AD) on friction-related disease (FRD).MethodsCross-sectional comparative study. This study included 550 eyes (550 patients) with dry eye disease (DED). The DED subtype and dynamic tear-film parameters by automated assessments were investigated for the analysis of FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy).ResultsPatients with FRD had a higher proportion of moderate-to-severe MGD and AD (p < 0.001 and p < 0.001, respectively). The dropout rate of the meibomian gland was higher (30.5 ± 31.8 and 14.1 ± 25.0%, p < 0.001), tear meniscus height (TMH) was lower (227.8 ± 60.4 and 241.7 ± 55.6 μm, p = 0.008), and he first non-invasive keratographic tear break-up time (NIKBUT-1) was shorter (5.9 ± 3.5 and 7.3 ± 3.7 s, p < 0.001) in patients with FRD than in those without FRD. In the logistic regression analysis with clinical manifestation, both moderate-to-severe MGD and AD were associated with FRD (odds ratios [OR] 12.27, 95% confidence interval [CI] 7.72–19.50, and 2.31, 95% CI 1.43–3.71], p < 0.001 and p < 0.001, respectively). The dropout rate was positively associated with FRD (OR 1.017, 95% CI 1.010–1.023, p < 0.001). TMH and NIKBUT-1 were negatively associated with FRD (OR 0.995, 95% CI 0.991–0.999, and 0.90, 95% CI 0.85–0.95, p = 0.039 and p < 0.001, respectively).ConclusionsThis study showed that FRD was highly associated with MGD and meibomian gland dropout rate, suggesting that FRD may be mainly affected by lipid components. AD and TMH also had a good but relatively lower association with FRD, compared to MGD and meibomian gland dropout rate.     

Tomografía de coherencia óptica de segmento anterior de alta resolución como método de diagnóstico diferencial entre neoplasia intraepitelial córneo-conjuntival y pterygium

ObjectiveTo assess if anterior segment optical coherence tomography (AS-OCT) is a noninvasive diagnostic method suitable to differentiate benign corneo-conjunctival lesions (pterygium) from premalignant lesions (corneo-conjunctival intraepithelial neoplasia, CIN).Material and methodsAn observational, analytical and cross-sectional study was conducted in 22 eyes with conjunctival lesions clinically suspicious for pterygium and CIN during two years. Morphological differences between both lesions were studied with AS-OCT; epithelial thicknesses (EE) and extension length on corneal surface (GIC) were compared between both groups. A surgical excision of the lesion was performed for histopathological diagnosis.ResultsMean age of patients with pterygium (n = 18) was 52.67 ± 15 y.o and 74 ± 12 y.o in subjects with CIN (n = 4) (p < 0.021). In pterygia, AS-OCT showed typical features (normal, thinning or slightly thickened EE; 77.4 ± 26 μm), in addition to an increase in wedge-shaped subepithelial tissue. Patients with CIN had a mean thickened EE (262.5 ± 124 μm) and strongly hyperreflective, with abrupt transition between normal and pathological epithelium. Analysis of EE between subjects with pterygium and CIN revealed statistically significant differences (p < 0.002). ROC curve revealed a 100% sensitivity and specificity of OCT-SA in differentiation between CIN and pterygium, using 141 μm as cutoff point of EE.ConclusionAS-OCT is a useful tool for the differentiation between pterygium and CIN able to provide typical morphological characteristics. An EE greater than 141 μm in AS-OCT suggests a sensitivity and specificity of 100% for the diagnosis of CIN.     

The use of high resolution optical coherence tomography (HR-OCT) in the diagnosis of ocular surface masqueraders

IntroductionOcular surface masqueraders encompass any ocular surface lesion masquerading as another ocular surface lesion. High resolution optical coherence tomography (HR-OCT) has emerged as an adjunctive tool to clinical acumen. This study's purpose is to evaluate the utility of HR-OCT images in guiding the diagnosis and management of those lesions.Material and methods22 individuals with a clinically ambiguous ocular surface lesion with slit lamp photographs (SLP), HR-OCT images, and histopathological examination were included in the study. The presumptive clinical diagnosis based on SLP was compared to the diagnosis suggested by HR-OCT findings and to definitive diagnosis by histopathology. The main outcome of this study was the frequency in which HR-OCT findings guided the clinician to the correct diagnosis.Results7 lesions were epithelial, 3 had an epithelial and a subepithelial component, and 12 were subepithelial. HR-OCT was most effective in discerning lesion location, successfully identifying the location in 100% of cases. Classic HR-OCT findings were detected in 68.2% of cases while suggestive features were detected in 31.8% of cases. The epithelial lesions' mean epithelial thickness was 265.4 ± 140.6 μm, the subepithelial lesions' mean was 58.0 ± 25.0 μm, and the combined lesions’ mean was 140.0 ± 70.0 μm. The epithelium was significantly thicker in epithelial lesions compared to subepithelial and combined lesions. By ROC analysis we identified that using a cut off of 156 μm, the sensitivity was 86% and the specificity was 93%.DiscussionHR-OCT can be a valuable diagnostic tool, assisting in the differentiation of ambiguous ocular surface pathologies by providing a cross-sectional, morphological image of the lesion.     

Ocular pain in ocular graft-versus-host disease patients with neurotrophic keratopathy

PurposeNeurotrophic keratopathy (NK) is a degenerative disorder of the cornea characterized by decreased sensory innervation, epitheliopathy, and impaired epithelial healing. In this study, we assessed ocular pain and quality-of-life-related parameters in ocular graft-versus-host disease (oGVHD) patients with and without NK.MethodsWe included 213 oGVHD patients in this retrospective study, including 29 patients with NK assessed by the Cochet-Bonnet esthesiometer. We evaluated their records for ocular pain assessment survey (OPAS) scores and clinical parameters, including corneal sensation, corneal fluorescein staining (CFS) score, Schirmer's test, tear break-up time (TBUT), and ocular surface disease index (OSDI) score.ResultsoGVHD patients with NK had lower corneal sensation (3.4 ± 1.4 vs. 5.9 ± 0.3; p < 0.0001), higher CFS scores (6.4 ± 4.2 vs. 4.7 ± 4.0; p = 0.01), and lower TBUT scores (1.2 ± 2.1 vs. 2.2 ± 3.1; p = 0.08) compared to oGVHD patients without NK and additionally had significantly higher ocular pain intensity scores (OPAS 24-h average eye pain intensity: 2.0 ± 2.8 vs. 1.1 ± 1.9; p = 0.03). Patients with NK more commonly reported burning (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.021) and sensitivity to light (0.2 ± 0.3 vs. 0.3 ± 0.4; p = 0.049) as compared to patients without NK.ConclusionClinical signs of ocular surface disease are worse in oGVHD patients with NK compared to oGVHD patients without NK. These patients additionally experience higher intensity ocular pain and lower quality-of-life-related parameters.     

Meibomian gland dysfunction is the primary determinant of dry eye symptoms: Analysis of 2346 patients

PurposeTo determine relative contributions of various ocular surface clinical signs and predisposing factors to the magnitude of dry eye symptoms.MethodsClinical audit data were prospectively collected for newly referred dry eye patients. All 2346 patients had an initial visit evaluation of the Ocular Surface Disease Index (OSDI), and a detailed ophthalmic examination including tear breakup time (TBUT), ocular surface fluorescein staining, Schirmer's I test. Among the participants, 1414 had number of liquid meibum expressing glands (NLMEG) evaluated on standard force expression. Other variables collected included history of glaucoma or glaucoma surgery, and history of allergies.ResultsIn patients aged 46.2 ± 14.8 years, 77.4% were women and 87.1% Chinese. The mean ± SD OSDI was 35.2 ± 21.7. On univariate analysis, higher OSDI was associated with glaucoma diagnosis (p = 0.003), glaucoma surgery (p = 0.002), greater temporal corneal staining (p = 0.002), reduced NLMEG (p < 0.001), and higher inferior forniceal papillary grade (p < 0.001). OSDI was not significantly associated with gender, TBUT, Schirmer's I test values, or the use of cyclosporine eyedrops. On multivariate regression, higher OSDI scores were associated with fewer NLMEG (p = 0.002) and increased lower eyelid forniceal papillary grading (p = 0.002). Corneal staining, glaucoma status and glaucoma surgery were not significantly associated with OSDI. Logistic regression showed that severe symptoms (OSDI>32) was associated with <2 NLMEG [OR(95%CI): 1.34(1.08–1.66)], and presence of inferior eyelid forniceal papillae [1.50(1.17–1.91)].ConclusionsMeibomian gland dysfunction (MGD) and lower forniceal papillary reaction had significant contributions to the severity of symptoms, in contrast to traditional dry eye signs. MGD should be objectively assessed and treated to improve symptoms.     

Implante de dexametasona antes de tratamiento anti-VEGF en desprendimientos del epitelio pigmentario secundarios a degeneración macular asociada a la edad con características de alto riesgo de rotura

ObjectiveEvaluate the incidence of pigment epithelial tear when intravitreal delayed-release dexamethasone implant is administered (off-label use) prior to antiangiogenic treatment in pigment epithelium detachments (PED) secondary to neovascular age-related macular degeneration (nAMD) with high-risk rupture characteristics and investigate if it causes a decrease in the PED size.MethodsPatients with nAMD, PED height > 500 microns and Ozurdex implant prior to the antiangiogenic therapy were included. The presence of pigment epithelium rupture in optical coherence tomography scans, best-corrected visual acuity (BCVA) and PED measurements (maximum height and diameter) were registered.ResultsThe study included 14 eyes of 14 patients: mean age 77 ± 7 years, 11 (79%) females. 25 ± 13 days after the Ozurdex, patients started with at least 3 anti-VEGF monthly injections. BCVA improved from 64 ± 14 to 69 ± 11 letters after anti-VEGF therapy (P > .05). Mean baseline PED height was 817 ± 269 μm, being 639 ± 268 μm after Ozurdex and 370 ± 260 μm after anti-VEGF injections (P = .035 and P = .009). One retinal pigment epithelium tear occurred (7%). No other adverse effects were reported.ConclusionsDexamethasone implant prior to anti-VEGF therapy may represent a promising therapeutic modality for large PED in nAMD, reducing PED dimensions and the risk of pigment epithelium tears prior to anti VEGF therapy.     

Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease

PurposeTo determine the prevalence, clinical characteristics, and risk factors associated with neurotrophic keratopathy (NK) in patients with chronic ocular graft-versus-host disease (oGVHD).DesignRetrospective cohort study.MethodsWe performed a chart review of patients diagnosed with chronic oGVHD between January 2015 and December 2018 at a single academic institution and recorded demographic data, systemic and ocular comorbidities, history of hematologic malignancy, transplant characteristics, oGVHD severity scores, and adnexal and ocular examination findings. We determined the prevalence of NK and clinical characteristics associated with NK in these patients. A multivariate logistic regression analysis was performed to determine the risk factors associated with NK in these patients.Main outcome measurePrevalence of NK in chronic oGVHD.ResultsWe identified 213 patients diagnosed with chronic oGVHD following hematopoietic stem cell or bone marrow transplantation from our electronic patient database, and the prevalence of NK was 14%. The mean age of oGVHD patients with NK was 62.6 ± 12.9 years; 48% were women, 19 had unilateral NK, and ten had bilateral NK. In the cohort, 56%, 20%, and 24% eyes of the patients had grades 1, 2, and 3 of NK, respectively. The mean time to diagnose NK after transplantation was 52.9 ± 45.4 months. oGVHD patients diagnosed with NK had a significantly higher NIH oGVHD severity score (p = 0.04) and a lower corneal sensation score (p = 0.0001) than those without NK. Our analyses showed a significantly higher CFS score (p = 0.01) and a trend toward lower Schirmer test scores (p = 0.16) and tear break-up times (p = 0.08) in oGVHD patients with NK. Additionally, we observed a significantly higher prevalence of persistent epithelial defect (p = 0.0001), corneal ulceration (p = 0.0001), and corneal perforation (p = 0.005) in oGVHD patients diagnosed with NK. A logistic regression analysis to determine factors associated with NK showed that a higher NIH oGVHD score (odds ratio [OR] = 2.03, p = 0.026) and history of cataract surgery (odds ratio [OR] = 5.03, p = 0.001) are significant risk factors for NK in oGVHD patients.ConclusionsThe prevalence of NK in chronic oGVHD patients was 14% during the study period. Our analysis shows that oGVHD patients with a higher NIH oGVHD severity score and previous history of cataract surgery are at a higher risk of developing NK and may develop severe sequelae such as persistent epithelial defect or corneal ulceration.     

Central corneal thickness measurement by Fourier domain optical coherence tomography,ocular response analyzer and ultrasound pachymetry

PurposeTo assess the repeatability, reproducibility, and agreement of central corneal thickness (CCT) measured by non-contact Fourier domain optical coherence tomography (FD-OCT; OptoVue) with the other two contact devices, ocular response analyzer (ORA; Reichert Ophthalmic Instruments) and Ultrasound Pachymetry (USP; DGH Technologies).MethodsThis observational cross-sectional study measured CCT sequentially using FD-OCT, ORA and USP. The first 16 volunteers (32 eyes) received three measurements by two independent examiners in a single session to determine intra-observer repeatability and inter-observer reproducibility. An additional 27 volunteers (54 eyes) received one measurement by the same examiner. The measurements of all 86 eyes were analyzed for the difference, correlation, and agreement among the three devices.ResultsFD-OCT measured the thinnest while USP measured the thickest CCT (548.6 ± 28.3 μm, 556.9 ± 28.8 μm, and 560.0 ± 28.8 μm by FD-OCT, ORA, and USP, respectively, p < 0.001). The mean differences (lower/upper limit of agreement) for CCT measurements were 8.4 ± 7.6 μm (−6.5/23.2) between ORA and FD-OCT, 11.4 ± 7.3 μm (−2.8/25.7) between USP and FD-OCT, and 3.1 ± 5.1 μm (−6.9/13.1) between ORA and USP. The intra-class correlation coefficients were above 0.98 for all tested groups. FD-OCT had the lowest intra-examiner variability (coefficient of repeatability of 0.64%) and lowest inter-examiner variability (coefficient of reproducibility of 1.16%).ConclusionFD-OCT, ORA, and USP demonstrated good inter-observer reproducibility and intra-observer repeatability. The three measurements were highly correlated; however, systematic differences between the three tested devices did exist. FD-OCT was a reliable and examiner-independent method in CCT measurement.     

Visualization of microneuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?

PurposeThe diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM).MethodsThis was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density.ResultsThere was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm²) and DED patients (12.86 ± 1.04 mm/mm²), as compared to normal controls (23.90 ± 0.92 mm/mm²; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm²) and DED patients (111.5 ± 23.86 cells/mm²), as compared to normal controls (24.81 ± 4.48 cells/mm² (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31).ConclusionIVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.     

Intravitreous injection of bevacizumab for chronic central serous chorioretinopathy

Background/PurposeTo evaluate the effect of intravitreal bevacizumab on subretinal fluid absorption in patients with chronic central serous chorioretinopathy (CSCR).Materials and methodsThis was a retrospective case series study. Patients with CSCR symptoms for > 3 months and who received intravitreal injection of bevacizumab were included. Ocular examinations were carried out at baseline and every follow-up visit, including visual acuity, fundus examination, and optic coherence tomography.ResultsTwelve eyes in 12 patients were included in this study. One month after injection, three of the 12 patients who had increased central macular thickness were considered nonresponders. Nine of the 12 patients who had decreased central macular thickness were considered to have responded to intravitreal bevacizumab injection. The response rate was 75%. In the response group, the mean central macular thickness significantly decreased, from 306.7 ± 77.8 μm to 204.3 ± 59.3 μm (p = 0.001) at 1 month. The mean Logarithm of the Minimum Angle of Resolution (logMAR) visual acuity was significantly improved from 0.72 ± 0.35 to 0.50 ± 0.28 (p = 0.008). Six of these nine patients had stable conditions lasting > 6 months. Three of them had recurrence.ConclusionIntravitreal bevacizumab injections improved subretinal fluid absorption in some patients with CSCR. It could be an alternative therapy for patients with CSCR, especially when they are not suitable for other treatments.     

Comparison of central corneal thickness measurements by Pentacam,noncontact specular microscope,and ultrasound pachymetry in normal and post-LASIK eyes

PurposeTo compare central corneal thickness (CCT) measurements taken with Pentacam, noncontact specular microscope (NCSM), and ultrasound pachymetry (US) in normal and post-laser in situ keratomileusis (LASIK) eyes and to assess the agreement between the three devices.DesignProspective clinical trial.Patients and methodsCentral corneal thickness (CCT) was measured in 94 eyes of normal volunteer and in 72 eyes of post-LASIK patients. Measurements were made with the three devices.ResultsIn normal eyes, the mean (±SD) CCT taken with Pentacam, NCSM, and US was 552.6 ± 36.8 μm, 511.9 ± 38.6 μm, and 533.3 ± 37.9 μm, respectively. The average values of CCT taken with the three instruments were significantly different. In post-LASIK eyes the mean CCT with Pentacam, NCSM, and US was 483.02 ± 6.03 μm, 450.7 ± 5.3 μm, and 469.5 ± 5.8 μm, respectively. The average values of CCT taken were significantly different for Pentacam vs. NCSM (P = 0.046) and Pentacam vs. US (P = 0.02), but not significant for NCSM vs. US (P = 0.352). The Bland and Altman method for assessing clinical agreement between 3 instruments showed that in normal eyes, the mean values and paired differences of the three CCT devices were found to be statistically independent. In post-LASIK eyes, there was significant association between the difference and the mean of the Pentacam and NCSM, and US and NCSM.ConclusionThe three devices cannot be used interchangeably in normal and post-LASIK eyes. Pentacam tends to give significantly thicker reading than ultrasound pachymetry.     

Chronic ocular complications in lamotrigine vs. trimethoprim-sulfamethoxazole induced Stevens-Johnson syndrome/toxic epidermal necrolysis

PurposeThe purpose of this study is to compare the severity of chronic ocular complications of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) induced by lamotrigine (LT) vs. trimethoprim-sulfamethoxazole (TS).MethodsThis retrospective cross-sectional study evaluated all SJS/TEN patients treated within our hospital network from 2008 to 2018. Inclusion criteria included patients with reactions identified as caused by either LT or TS, and patients with at least one ophthalmology follow up in the chronic phase (≥3 months from disease onset). Primary outcome measures included LogMAR best-corrected VA at most recent visit and the presence or absence of severe ocular complications (SOC). Secondary outcome measures included chronic ocular complication severity scores using a modified Sotozono scoring system.ResultsForty-eight eyes of 24 patients were included in the study. The mean duration of follow-up was 39.50 ± 35.62 vs. 48.17 ± 33.09 months, respectively (p = 0.482). The LT group had worse average VA at the most recent visit (LogMAR VA; 0.508 vs. 0.041, p < 0.0001) and had a higher prevalence of SOCs (66.7% vs. 8.3%, p = 0.0038). The LT group scored worse on Sotozono chronic complications scores for the cornea (1.875 vs. 0.5, p = 0.0018), eyelid margin (5.583 vs.3.083, p = 0.0010), and overall condition (8.500 vs. 4.833, p = 0.0015). Sub-analyses showed that a moderate or severe acute ocular severity score was a significant predictor of chronic outcomes.ConclusionsCompared to patients with TS-induced SJS/TEN, patients with LT-induced SJS/TEN developed worse chronic ocular complications on several parameters. Future prospective studies are warranted to provide additional insight into the drug type as a predictor of chronic ocular complications.     

Hallazgos tempranos por microscopia confocal en cross-linking

ObjectiveTo determine the effects of in vivo cross-linking treatment of the cornea.MethodsEighteen eyes of eighteen keratoconus patients underwent cross-linking treatment using a 0.1% riboflavin solution and ultraviolet A radiation at 370 nm at 3 mW/cm² for 30 minutes. In vivo confocal microscopy was performed before, and at 1 week and 1 month after treatment.ResultsAt 1 week after treatment, keratocyte activation and collagen fiber organization showed as hyper-reflective structures and were observed from the first sub-epithelial image to a corneal stromal depth of 275.1 ± 85.9 μm. At 1 month after treatment, activated keratocytes and fiber organization were also observed from the first sub-epithelial image to a corneal stromal depth of 324.9 ± 66.0 μm. The deepest hyper-reflective structures at 1 month showed as thick, linear-shaped hyper-reflective structures.ConclusionIn vivo confocal microscopy in humans showed corneal stromal changes at 1 week and 1 month after cross-linking treatment, in some cases at depths in excess of 300 μm.