A deep learning approach to investigate the filtration bleb functionality after glaucoma surgery: a preliminary study.

PURPOSE: To distinguish functioning from failed filtration blebs (FBs) implementing a deep learning (DL) model on slit-lamp images. METHODS: Retrospective, cross-sectional, multicenter study for development and validation of an artificial intelligence classification algorithm. The dataset consisted of 119 post-trabeculectomy FB images of whom we were aware of the surgical outcome. The ground truth labels were annotated and images splitted into three outcome classes: complete (C) or qualified success (Q), and failure (F). Images were prepared implementing various data cleaning and data transformations techniques. A set of DL models were trained using different ResNet architectures as the backbone. Transfer and ensemble learning were then applied to obtain a final combined model. Accuracy, sensitivity, specificity, area under the ROC curve, and area under the precision-recall curve were calculated to evaluate the final model. Kappa coefficient and P value on the accuracy measure were used to prove the statistical significance level. RESULTS: The DL approach reached good results in unraveling FB functionality. Overall, the model accuracy reached a score of 74%, with a sensitivity of 74% and a specificity of 87%. The area under the ROC curve was 0.8, whereas the area under the precision-recall curve was 0.74. The P value was equal to 0.00307, and the Kappa coefficient was 0.58. CONCLUSIONS: All considered metrics supported that the final DL model was able to discriminate functioning from failed FBs, with good accuracy. This approach could support clinicians in the patients' management after glaucoma surgery in absence of adjunctive clinical data.

Epiretinal membrane development after Ex-Press glaucoma filtration device implant: 2-year results of a case control study.

BACKGROUND: The most common retinal complications after glaucoma surgery are choroidal detachment, hypotony maculopathy, malignant glaucoma, vitreous hemorrhage, endophthalmitis and retinal detachment. However, if glaucoma surgery is a risk factor for the ERM development needs to be clarified. This study aims to assess the incidence of epiretinal membrane (ERM) in 2 years of follow-up in patients with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. METHODS: A prospective, consecutive, single-center, case-control study. We enrolled patients affected by POAG and scheduled for Ex-Press device implant with or without concomitant cataract surgery. The control group was the contralateral eyes which continues anti-glaucomatous eyedrops. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography were performed before surgery, at 6 months and 24 months of follow-up. RESULTS: Eighty-two eyes of 41 consecutive patients, 18 males and 23 females with a mean age of 70, 29 ± 8,45, were analyzed at 24 months. 39.1% of eyes developed ERM: 29.3% were cellophane macular reflex (CMR) and 9.8% were pre-macular fibrosis (PMF). In the control group, 19.5% of eyes developed ERM: 17.1% were CMR and 2.4% were PMF. No statistically significant difference was reported (p = 0.121) between treated and control group. ERM development did not affect significantly the central foveal thickness (260.13 ± 35.01 µm at baseline, 265.03 ± 34.90 µm at 6 months and 275.18 ± 33.31 µm at 24 months) and macular volume (7.75 ± 0.43 mm3 at baseline, 7.77 ± 0.48 mm3 at 6 months and 7.77 ± 0.46 mm3 at 24 months), remained comparable to reported average measures in healthy individuals during the follow-up. Concomitant cataract surgery did not increase the ERM incidence. CONCLUSION: Ex-Press implant may increase the ERM incidence regardless concomitant cataract surgery, accelerating or inducing a posterior vitreous detachment, such as other ocular surgical procedure. Nevertheless, the vast majority of ERM are CMR, not affecting the macular profile.

Short-term results of a pulsed therapy with hydrocortisone eye drops to treat moderate to severe dry eye in primary Sjögren syndrome patients.

BACKGROUND: We investigated the safety and efficacy of short-term treatment with topical low-dose hydrocortisone sodium phosphate 0.335% (PFH) in patients with moderate to severe primary Sjögren syndrome (SS)-related dry eye disease (DED). METHODS: A retrospective single-centre interventional study. All patients received PFH for 6 days with a pulsed posology: three times daily for 2 days, twice daily for 2 days, and once daily for 2 days. This scheme was repeated for 3 consecutive months and then alternated for 3 months. Data were collected at baseline, 3 months, and 6 months of follow-up. RESULTS: A total of 40 SS patients were enrolled. Conjunctival hyperaemia and corneal-conjunctival stain significantly improved (p < 0.001). Ocular Surface Disease Index score reduced significantly between baseline and 3 months and between baseline and 6 months (p < 0.001). The tear film osmolarity lowered significantly in each eye from baseline to 3 months and from baseline to 6 months (p = 0.002 and p = 0.037, respectively). Comparing results at 3 and 6 months, the Ocular Surface Disease Index score (p = 1.000), the frequency of lacrimal substitutes installation (p = 0.632), and tear film osmolarity (right eye p = 0.518, left eye p = 1.000) did not change significantly. Intraocular pressure did not change during the study period. CONCLUSION: PFH eye drops with a pulsed posology improve signs and symptoms, not affecting the intraocular pressure in SS-related DED. Therefore, this pulsed treatment is safe and efficacious.

Managing the ocular surface after glaucoma filtration surgery: an orphan topic.

BACKGROUND: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management. METHODS: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life. RESULTS: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL). CONCLUSIONS: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice.

In Vivo Confocal Microscopy of the Corneal Sub-Basal Nerve plexus in Medically Controlled Glaucoma.

The present study investigated the corneal sub-basal nerve plexus (SNP) modifications in glaucoma. Ninety-five glaucomatous patients were enrolled and divided into Group 1 and 2, preserved and preservative-free mono-therapy (30 and 28 patients), and Group 3, multi-therapy (37). Thirty patients with dry eye disease (DED) and 32 healthy subjects (HC) served as controls. In vivo confocal microscopy evaluated the nerve fibers density (CNFD), length (CNFL), thickness (CNFT), branching density (CNBD), and dendritic cell density (DCD). CNFD, CNFL, and CNBD were reduced in Group 3 and DED compared to HC (p < 0.05). CNFL was reduced in Group 3 compared to Group 2 (p < 0.05), and in Group 1 compared to HC (p < 0.001). CNFD, CNBD, and CNFT did not differ between glaucomatous groups. DCD was higher in Group 3 and DED compared to HC and Group 2 (p < 0.01). Group 3 showed worse ocular surface disease index (OSDI) scores compared to Group 1, 2, and HC (p < 0.05). CNFL and DCD correlated with OSDI score in Group 3 (r = −0.658, p < 0.001; r = 0.699, p = 0.002). Medical therapy for glaucoma harms the corneal nerves, especially in multi-therapy regimens. Given the relations with the OSDI score, SNP changes seem features of glaucoma therapy-related OSD and negatively affects the patient's quality of life.

Beneficial effect of low-dose radioiodine ablation for Graves' orbitopathy: results of a retrospective study.

OBJECTIVE: Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS: Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS: The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS: The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.

Secondary epiretinal membrane after Ex-Press glaucoma filtration device implant.

PURPOSE: To estimate the frequency of epiretinal membrane (ERM) in eyes with primary open-angle glaucoma (POAG) treated with Ex-Press shunt implant. Secondarily, we aimed to assess the role of concomitant cataract surgery and the impact of the ERM on central foveal thickness and macular volume. METHODS: In this prospective, consecutive, case-control study, we enrolled 54 patients affected by PAOG and scheduled for Ex-Press device implant with or without contemporary phacoemulsification. Contralateral eyes affected by POAG and receiving anti-glaucomatous eyedrops constituted the control group. Complete ophthalmologic evaluation and spectral-domain optical coherence tomography (OCT) were performed before and 1, 3 and 6 months after surgery. RESULTS: Twenty-six eyes received the Ex-Press implant alone, and 28 eyes underwent the combined procedure. Six months postoperatively, we observed 18 (33%) cases of ERM: 15 (28%) of cellophane macular reflex (CMR) and 3 (6%) of pre-macular fibrosis (PMF). In the control group, 9 (17%) eyes developed an ERM: 8 (15%) were CMR, and 1 (2%) was PMF. The frequency of ERM statistically differs between treated and contralateral eyes (P = 0.032, χ2 test). The ERM frequency did not statically differ between eyes subjected to simple or combined surgery (P = 0.846, χ2 test). Mean central foveal thickness and mean macular volume did not significantly differ between groups. CONCLUSION: The Ex-Press glaucoma shunt may increase the risk of ERM onset regardless of the concomitant cataract surgery; however, most cases were cellophane macular reflex with limited functional and anatomical impact.

Behçet's syndrome and ocular involvement: changes over time.

Ocular involvement in Behçet's syndrome still represents a challenge for both rheumatologists and ophthalmologists; over the past 20 years the availability of new diagnostic tools and the concomitant introduction of biologic drugs led to a significant improvement in the management of these patients. The lack of uniform definitions and the diversity of the outcome measures still represent an obstacle for the prompt and correct management of ocular manifestations. The aim of the present review is to summarise the current evidences related to correct diagnosis and proper management of patients with Behçet's syndrome and ocular involvement.

Aqueous humour concentrations after topical apPlication of combinEd levofloxacin-dexamethasone eye dRops and of its single components: a randoMised, assEssor-blinded, parallel-group study in patients undergoing cataract surgery: the iPERME study.

PURPOSE: To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery. METHODS: Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis. RESULTS: A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8-4.2 · 10-4 for levofloxacin and 0.3-0.4 · 10-4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone. CONCLUSION: Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03740659.

Pachychoroid neovasculopathy: a type-1 choroidal neovascularization belonging to the pachychoroid spectrum-pathogenesis, imaging and available treatment options.

PURPOSE: The purpose of this paper is to provide a meaningful literature review about the epidemiology, pathogenesis, imaging and treatment of pachychoroid neovasculopathy (PNV). METHODS: A computerized search from inception up to December 2019 of the online electronic database PubMed was performed using the following search string: "pachychoroid neovasculopathy". The reference list in each article was scanned for additional relevant publications. RESULTS: PNV is a type-1 choroidal neovascularization, overlying focal areas of choroidal thickening and dilated choroidal vessels. It can develop in patients affected by pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy. The absence of drusen, the presence of pachydrusen, younger age of onset and choroidal thickening distinguish it from neovascular age-related macular degeneration (AMD). PNV incidence and prevalence data are lacking. Its pathophysiology is not fully understood, but angiogenic mechanisms involved in neovascular AMD may be different from those in PNV. Due to optical coherence tomography (OCT) improvements, PNV can be diagnosed more easily than before. In particular, PNV shows a shallow pigment epithelium detachment with an undulating retinal pigment epithelium over a subfoveal choroidal thickening, associated with vein enlargement in Haller's layer (named pachyvessels) and choriocapillaris thinning. On OCT angiography, PNV reveals tangled hyper-reflective filamentous neovessels in the choriocapillaris itself. The current first-line PNV treatment is intravitreal anti-VEGF (vascular endothelial growth factor) injections with a treat-and-extend regimen. In particular, aflibercept shows a higher rate of fluid absorption than others. In the case of fluid recurrence or persistence, photodynamic therapy is a valid alternative. CONCLUSION: Ongoing research into pathophysiology and imaging improvements may be helpful in defining prognostic criteria and stratifying patient risk, allowing responsible monitoring and management of PNV.

Retinal, choroidal and optic disc analysis in patients with Graves' disease with or without orbitopathy.

PURPOSE: To compare optic disc, retinal and choroidal measurements in patients with Graves' disease with or without orbitopathy, and healthy controls. METHODS: Optical coherence tomography and Heidelberg retinal tomography were performed in 40 patients with Graves' orbitopathy (GO), 40 subjects with Graves's disease (GD) with no sign of orbitopathy and 40 healthy controls. Degree of exophthalmos, ocular alignment, clinical activity score (CAS), choroidal thickness, retinal thickness, ganglion cell layer (GCL) thickness, disc area, cup area, rim area, cup/disc area ratio, linear cup/disc ratio and mean peripapillary retinal nerve fibre layer thickness were analysed. RESULTS: GO patients and healthy controls significantly differ regarding mean central retinal thickness (275 ± 19 µm and 285 ± 20 µm, P = 0.017); mean central GCL thickness (14.87 ± 3.0 µm and 17.92 ± 5.02 µm, P = 0.001); mean disc area (2.00 ± 0.44 mm2 and 1.72 ± 0.37 mm2, P = 0.003); mean cup area (0.53 ± 0.52 mm2 and 0.31 ± 0.20 mm2, P = 0.003); cup/disc area ratio (0.22 ± 0.10 and 0.17 ± 0.08, P = 0.010); and linear cup/disc ratio (0.47 ± 0.15 and 0.40 ± 0.13, respectively, P = 0.011). No difference was found between patients without orbitopathy and healthy controls. No significant difference was found regarding the choroidal thickness between the three groups. There was no statistically significant relationship between retinal thickness, ganglion cell layer thickness, mean disc area, mean cup area, cup/disc area ratio, linear cup/disc ratio, CAS, exophthalmometric value and ocular alignment. CONCLUSION: GO patients showed significant changes in foveal and GCL thickness, and optic nerve head morphology suggesting a possible influence of the orbital inflammatory process.

Effect of Resveratrol on In Vitro and In Vivo Models of Diabetic Retinophathy: A Systematic Review.

A large number of preclinical studies suggest the involvement of resveratrol in the prevention and treatment of eye diseases induced by oxidative stress and inflammation. We tested the hypothesis that resveratrol influences many pathways of in vitro and in vivo models of diabetic retinopathy through a systematic literature review of original articles. The review was conducted in accordance with the PRISMA guidelines. A literature search of all original articles published until April 2019 was performed. The terms "resveratrol" in combination with "retina", "retinal pathology", "diabetic retinopathy" and "eye" were searched. Possible biases were identified with the adopted SYRCLE's tool. Eighteen articles met inclusion/exclusion criteria for full-text review. Eleven of them included in vitro experiments, 11 studies reported in vivo data and 3 studies described both in vitro and in vivo experiments. Most of the in vivo studies did not include data that would allow exclusion of bias risks, according to SYRCLE's risk of bias tool. Both in vitro and in vivo data suggest anti-apoptotic, anti-inflammatory and anti-oxidative actions of resveratrol in models of diabetic retinopathy. However, results on its anti-angiogenic effects are contradictory and need more rigorous studies.

Macular spectral-domain optical coherence tomography values and correlations in healthy children.

PURPOSE: The aim of this study is to investigate potential correlations between age, gender, spherical equivalent and optical coherence tomography (OCT) retinal parameters among healthy children. METHODS: A macular spectral-domain OCT was performed in all patients using a Spectralis® OCT device, and the macular thickness and volume of each of the early treatment diabetic retinopathy study (ETDRS) subfields were analysed. RESULTS: Ninety-four children were enrolled. Mean central macular thickness was 274.968 ± 18.28 µm, while mean central macular volume was 0.216 mm3. Statistical analysis showed a significant correlation between the factor age and central macular thickness (F(3,90) = 4.96, p = 0.003, η2 = 0.14) and central macular volume (F(3,90) = 4.98, p = 0.003, η2 = 0.14). Statistical analysis showed a significant correlation between the factor gender and macular thickness/volume of several ETDRS subfields. A significant correlation between refractive error and macular thickness/volume was also noted. CONCLUSIONS: This study shows significant correlations between macular thickness/volume and the factors age, gender and spherical equivalent. Paediatric spectral-domain optical coherence tomography ranges need further investigations since many significant correlations are still to be confirmed.

INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR MACULAR HOLE SURGERY WITHOUT EXTRA MANIPULATION OF THE FLAP.

PURPOSE: To determine whether surgical manipulation steps of the internal limiting membrane (ILM) flap, such as ILM trimmed, ILM tuck inside the hole, ILM massage, are mandatory to obtain satisfactory outcomes for the repair of large stage IV idiopathic macular hole using the inverted ILM flap technique. METHODS: In this interventional comparative prospective single-masked study, 81 eyes were randomized into 2 treatments groups. In Group 1 (41 eyes), the classic inverted ILM flap technique was performed. In Group 2 (40 eyes), a modified procedure was used: after ILM peeling, no extra flap manipulation was performed. The macular hole was covered by the inverted ILM flap because of the air pressure at the time of the fluid-air exchange. RESULTS: At 12 months, macular hole closure was observed in 40 eyes (97.6%) in Group 1 and in 39 eyes in Group 2 (97.5%). U-shape closure rate, ellipsoid zone defects, and external limiting membrane defects were similar in both groups. The results indicate no statistical difference in anatomical and functional success between both groups. CONCLUSION: The macular hole closure rate, improved visual acuity, and no extra complications indicate noninferiority of the modified inverted ILM technique. Internal limiting membrane finishing, tucking, and massage may not be required to obtain surgical success.

Analysis of Choroidal Thickness Change after 25-Gauge Vitrectomy for Idiopathic Epiretinal Membrane with or without Phacoemulsification and Intraocular Lens Implantation.

PURPOSE: This study aimed to evaluate choroidal thickness modifications before and after vitrectomy with or without phacoemulsification for idiopathic epiretinal membrane in the operated eye and in the unaffected fellow eye. METHODS: In total, 53 eyes of 53 patients underwent 25-gauge pars plana vitrectomy plus internal limiting membrane peeling and air tamponade. Twenty-seven eyes underwent combined surgery with phacoemulsification and intraocular lens implantation. Choroidal thickness was measured using enhanced deep image spectral-domain optical coherence tomography at the fovea and at 500 and 2,500 µm from the fovea. Fellow eyes without any previous ocular surgery history served as controls. RESULTS: Baseline comparison did not show significant differences between study and fellow eyes (p > 0.05). Choroidal thickness significantly decreased in the subfoveal area (p = 0.004) as well as at 500 µm (p = 0.026) and 2,500 µm nasally (p = 0.019) and at 500 µm (p = 0.039) and 2,500 µm (p = 0.005) temporally to the fovea. No significant changes were observed postoperatively in the superior and inferior areas (p > 0.05). No differences were found between eyes which underwent combined surgery and those which underwent vitrectomy alone (p > 0.05). The unaffected eyes did not show any significant changes (p > 0.05). CONCLUSIONS: Comparison of baseline values did not show any differences between affected and unaffected eyes, meaning that choroidal thickness was not influenced by the development of epiretinal membrane. Vitrectomy plus epiretinal and inner limiting membrane removal may influence choroidal homeostasis, leading to a decrease in choroidal thickness in the subfoveal, nasal, and temporal areas. Combined surgery did not show significant differences when compared to vitrectomy alone.

Intravitreal ranibizumab for predominantly hemorrhagic choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the effects of intravitreal ranibizumab monotherapy on predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. MATERIALS AND METHODS: Twenty-two consecutive eyes with hemorrhagic neovascularization were treated with 3 monthly intravitreal ranibizumab injections. Additional injections were administered according to retreatment criteria during 12 months of follow-up. RESULTS: A mean of 6.64 ± 1.36 injections was administered. Overall, the mean visual acuity increased from 10.90 ± 6.02 to 12.81 ± 8.34 ETDRS letters (p > 0.05) at 12 months. The 'early treatment group' gained a mean of 2.83 ± 2.24 ETDRS letters (p < 0.05), while the 'late treatment group' gained a mean of 0.30 ± 1.25 ETDRS letters (p > 0.05) with significant differences between the groups (p < 0.05). A progressive resolution of macular bleeding was registered in 20 patients (mean time: 5.3 ± 1.6 months). CONCLUSIONS: Ranibizumab injections can be considered a beneficial approach for the management of predominantly hemorrhagic choroidal neovascularization with foveal involvement associated with age-related macular degeneration. Furthermore, the time interval between hemorrhage and the first injection seems to be an important predicting factor of final visual acuity.

Changes in the morphological and functional patterns of the ocular surface in patients treated with prostaglandin analogues after the use of TSP 0.5%® preservative-free eyedrops: a prospective, multicenter study.

AIM: To investigate and compare the effects of topical benzalkonium chloride-preserved prostaglandins (PGAs) on the ocular surface in patients with primary open-angle glaucoma before and after 3 months of treatment with additional 0.5% preservative-free tamarind seed polysaccharide single-dose eyedrops (TSP®, Oftagen, Pisa, Italy). METHODS: This was a prospective, longitudinal, multicenter study. From 5 different Italian glaucoma centers, 10 glaucomatous patients were recruited in each center. All the patients were treated with a PGA with preservative for at least 1 year. Preservative-free artificial tears 3 times per day were prescribed. The participants were subjected to clinical and instrumental evaluation at baseline, after 1 month and after 3 months of treatment. All patients were examined with a digital corneal confocal laser scanning microscope (HRT II Rostock Cornea Module). RESULTS: After 3 months of TSP 0.5% treatment, an improvement of some ocular signs and symptoms was found. The percentage of conjunctival hyperemia decreased from 67 to 13%. Schirmer's test and breakup time significantly changed from the baseline after 3 months. Confocal microscopy showed a significant increase in conjunctival goblet cells. CONCLUSION: Artificial substitutes, in particular TSP 0.5%, might protect the ocular surface hence giving higher compliance, adherence and quality of life to the patients.

A pilot study on Langerhans cells in keratoconus patients by in vivo confocal microscopy before and after corneal cross-linking and correlation with eye rubbing.

PURPOSE: The aim of this study was to investigate the corneal microstructure and Langerhans cells using in vivo confocal microscopy in keratoconus patients before and after cross-linking, and to correlate the morphologic findings with clinical and patient-reported outcomes, including eye rubbing (ER) behavior. METHODS: Patients with progressive keratoconus undergoing iontophoresis-assisted epithelium-on cross-linking (I-CXL) were consecutively enrolled. In vivo confocal microscopy was performed before and 6 months after treatment. Patients were asked to quantify their ER behavior on a Visual Analogue Scale (VAS) and completed the Keratoconus Outcomes Research Questionnaire and the Ocular Surface Disease Index questionnaires at the same time points. Visual acuity, tear osmolarity, topography, aberrometry, and pachymetry of both eyes were assessed. RESULTS: Thirteen patients were included in this pilot study. Preoperatively, the mean Langerhans cells density was 35,615 cells per mm2, and the median morphology was 3. The mean ER VAS before treatment was 7,077 out of 10. The ER VAS showed significant positive correlations with both Langerhans cells density and morphology of the study eye. After treatment, a statistically significant reduction in ER VAS and in Langerhans cells variables was observed. The mean sub-basal plexus nerve density was comparable to pre-operative values 6 months after I-CXL. CONCLUSIONS: Based on this preliminary evidence, the presence of high density of mature Langerhans cells in the central cornea of keratoconus patients and its correlation with eye rubbing support the role of inflammation in keratoconus. The reduction in these markers after treatment may suggest a potential of CXL in moderating immune-related inflammation and eye rubbing in the medium term.