Unusual presentation of ocular surface squamous neoplasia in a young healthy patient: A case report.

PURPOSE: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient. CASE DESCRIPTION: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision. DISCUSSION: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity. CONCLUSION: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision.

The Orphan Drug for Acanthamoeba Keratitis (ODAK) Trial: PHMB 0.08% (Polihexanide) and Placebo versus PHMB 0.02% and Propamidine 0.1.

PURPOSE: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment. DESIGN: Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895). PARTICIPANTS: One hundred thirty-five patients treated at 6 European centers. METHODS: Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes. MAIN OUTCOME MEASURES: The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates. RESULTS: One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred. CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Beauveria bassiana Keratitis: A Case Series and Review of Literature.

BACKGROUND: Beauveria bassiana is a filamentous fungus commonly used as an insecticide that rarely causes keratitis. METHODS: Patients affected by Beauveria bassiana keratitis were retrospectively recruited at San Raffaele Hospital (Milan, Italy) between 2020 and 2022. All subjects underwent comprehensive ophthalmic evaluation, including in vivo confocal microscopy (IVCM) and microbiologic examination of corneal scrapings. Beauveria bassiana was identified using 18S rDNA targeted PCR. RESULTS: Four eyes of four patients (51 ± 8.8 years old) were evaluated. The main risk factors were soft contact lens wear (75%) and trauma with vegetative matter (50%). A superficial infiltrate was displayed in the majority of patients. Three cases (75%) showed hyphae on IVCM. All patients showed clinical improvement after topical antifungal therapy, although mostly through a combination of two antifungals (75%). One patient with a deeper infection required a systemic antifungal agent after one month of topical therapy. All cases required debridement to reduce the microbial load and enhance drug penetration. All patients experienced keratitis resolution following medical treatment (average: 3.3 months). CONCLUSIONS: The identification of risk factors and the early diagnosis of Beauveria bassiana keratitis are fundamental in order to avoid its penetration in the deeper corneal stromal layers. Topical antifungal drugs, possibly accompanied by ulcer debridement, may be a successful treatment if instilled from the early phases of the disease.

Safety and Efficacy of Corneal Cross-Linking in Patients Affected by Keratoconus: Long-Term Results.

The present study evaluated the effectiveness and safety of corneal collagen cross-linking (CXL). A total of 886 eyes with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standard epithelium-off Dresden protocol. Visual outcomes, maximum keratometry (Kmax), demarcation line measurements, and complications were recorded. Visual outcomes and keratometric data were analyzed in a subgroup comprising 610 eyes. Uncorrected distance visual acuity (UDVA) improved from 0.49 ± 0.38 LogMAR to 0.47 ± 0.39 LogMAR (p = 0.03, n = 610) three years after the procedure, while corrected distance visual acuity (CDVA) improved from 0.15 ± 0.14 LogMAR to 0.14 ± 0.15 LogMAR (p = 0.007, n = 610). A significant reduction of Kmax from 56.28 ± 6.10 to 54.98 ± 6.19 (p < 0.001, n = 610) was observed three years after CXL. In five eyes (0.82%, 5/610) keratoconus progression continued after CXL. Three eyes were retreated successfully with documented refractive and topographic stability after five years. In the 35 eyes that completed 10 years of follow-up, mean visual acuity and topographic parameters remained stable. In conclusion, CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure.

Refractive surgery and dry eye.

Refractive surgery is one of the most common elective surgeries performed worldwide. The incidence of dry eye disease (DED) after corneal refractive surgery varies among different studies. Pre-existing untreated DED has been identified as a risk factor for postsurgical dry eye symptoms. On the basis of both evidence and clinical experience, some recommendations for ocular surface and DED management pre- and post-refractive surgery are described. In aqueous deficiency Dry Eye Disease, preservative-free lubricating drops should be preferred, in addition to ointment and gel forms. Topical anti-inflammatory agents (Cyclosporine 0.1%, hydrocortisone phosphate, fluorometholone) should be used for 3-6 months in cases of ocular surface damage. The therapy of evaporative DED includes lifestyle modifications, lid hygiene (either performed by the patient or offered as professional lid hygiene by the physician), use of lubricating eye drops with lipid components, topical and/or systemic antibiotic treatment with anti-inflammatory properties and Intense Pulsed Light (IPL-) Treatment for meibomian gland dysfunction.

New Findings in Early-Stage Keratoconus: Lamina Cribrosa Curvature, Retinal Nerve Fiber Layer Thickness, and Vascular Perfusion.

PURPOSE: Our aim was to investigate the involvement of posterior pole structures in eyes affected by keratoconus (KC). Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to determine the status of lamina cribrosa (LC), peripapillary retinal nerve fiber layer (RNFL), macular and peripapillary microvasculature. DESIGN: Observational, cross-sectional, case-control analysis. METHODS: Single-center investigation involving patients with KC and healthy control subjects. Enrolled subjects underwent anterior segment OCT combined with Placido-disk topography, macular and optic nerve head swept-source OCT and swept-source OCTA scans, and 3D wide glaucoma module for peripapillary RNFL thickness measurement. The LC curvature index was used to express the degree of LC posterior bowing. We calculated the vessel density and vessel length density at the macular superficial capillary plexus, deep capillary plexus, choriocapillaris, and nerve radial peripapillary capillary plexus. RESULTS: Overall, 32 eyes with KC and an equal number of age- and axial length-matched control eyes were included in the analysis. Almost all (97%) of eyes with KC were classified as early stage. KC displayed a reduction in peripapillary RNFL thickness (104.8 ± 11.9 µm vs 110.7 ± 10.5 µm; P = .039) and nerve radial peripapillary capillary plexus vessel density (46.31% ± 3% vs 43.82% ± 4%; P = .006) when compared with control subjects; these differences were more evident in the temporal sector and were associated with a higher LC curvature index (9.9% ± 2.6% vs 8.48% ± 1.7%; P = .012). Mean macular superficial capillary plexus vessel density was 3 percentage points lower in eyes with KC than in healthy controls (P < .001). CONCLUSION: Early-stage KC may be characterized by a posterior bowing of the LC along with a subtle peripapillary RNFL thinning and vascular impairment. These findings support the hypothesis that KC may be a corneal manifestation of a more generalized "eye collagen disease."

Evaluation of a Post-Operative Therapy Protocol after Epithelium-Off Corneal Cross-Linking in Patients Affected by Keratoconus.

A large retrospective study evaluated the safety of a post-operative therapy protocol after epithelium-off corneal collagen cross-linking (CXL). In total, 1703 eyes of the 1190 patients with progressive keratoconus were enrolled in a retrospective cohort study in a tertiary care university hospital. CXL was performed using a standardized technique (Dresden protocol: 0.1% riboflavin solution containing dextran 20% for 30 min during the soaking phase followed by 30-min ultraviolet A irradiation (3 mW/cm2)). Postoperatively, a bandage contact lens was applied, and therapy included a topical fluoroquinolone antibiotic until the epithelium healed, followed by topical fluorometholone treatment for three weeks. Post-operative complications were recorded and analyzed. No cases of infectious keratitis occurred, whereas peripheral sterile infiltrates were observed in 1.17% of cases. Trace haze was typically present but did not have an impact on visual acuity. In fifteen cases (0.88%), visually significant anterior stromal opacity developed. Mild signs of dry eye were observed in 22 eyes (1.29%). The present study demonstrates that a post-operative treatment protocol including fluoroquinolone antibiotics and a BCL in the first phase until complete epithelial healing, followed by a three-week period of topical steroid treatment is safe and not associated with the development of microbial keratitis.

Vitamin D Supplementation Impacts Systemic Biomarkers of Collagen Degradation and Copper Metabolism in Patients With Keratoconus.

Purpose: To evaluate the impact of vitamin D (Vit D) supplementation on systemic biomarkers of collagen degradation, inflammation, oxidative stress, and copper metabolism in adolescent patients with keratoconus (KC). Methods: This was a prospective observational pilot study. Twenty patients (age range, 16-19 years) presenting KC and Vit D insufficiency (<30 ng/mL) were included. Vit D supplementation was prescribed by their general practitioner as per the standard of care. Patients were followed up for 12 months. At each visit, best spectacle-corrected visual acuity (BSCVA), maximal keratometry (Kmax), and thinnest corneal thickness (TCT) were evaluated. The primary outcome of the study was the proportion of patients with Kmax progression of less than 1 D throughout the 12-month follow-up time. Blood samples were collected at different time points to evaluate Vit D levels and systemic markers of collagen degradation, inflammation, oxidative stress, and copper metabolism by ELISA or RT-PCR. Results: Lower Vit D levels in the plasma were correlated with higher levels of systemic biomarkers of collagen degradation. Vit D supplementation increased the cell availability of copper. Moreover, stabilization of KC progression was found in 60% of patients (72% of eyes) after 12 months with Vit D supplementation. BSCVA, Kmax, and TCT rates remained stable during the observation period. Conclusions: Our findings support that Vit D administration could affect ocular and systemic biomarkers in KC and illuminate a possible mechanism that can be used to develop new treatment alternatives. Translational Relevance: Although KC therapy currently relies exclusively on surgical procedures, Vit D supplementation may offer a non-invasive and inexpensive alternative with minimal associated side effects.

IOL Power Calculation in Eyes Undergoing Combined Descemet Membrane Endothelial Keratoplasty and Cataract Surgery.

PURPOSE: To assess the accuracy of different corneal powers for intraocular (IOL) power calculation in combined Descemet membrane endothelial keratoplasty (DMEK) and cataract surgery and investigate whether preoperative parameters correlate to the prediction error (PE). METHODS: This prospective case series involved patients with Fuchs endothelial dystrophy receiving combined DMEK and cataract surgery. Preoperatively, patients underwent optical biometry and anterior segment OCT (AS-OCT). AS-OCT measurements were repeated 6 months postoperatively, when final refraction was assessed. The PE was calculated using the preoperative average keratometry (Kave) measured by the optical biometer and User Group for Laser Interference Biometry (ULIB) constants. It was also calculated, after constant optimization, using the preoperative Kave from both devices and the total corneal power (TCP) measured by AS-OCT, as well as the postoperative Kave and TCP measured by AS-OCT. RESULTS: ULIB constants resulted in the highest hyperopic PE (P < .0001). Constant optimization improved the results, because the PE was zeroed out and the absolute PEs decreased. No significant difference was found among the Barrett Universal II, Emmetropia Verifying Optical 2.0, Haigis, Hoffer Q, Holladay 1, Kane, and SRK/T formulas. Further improvement was achieved with the postoperative Kave and TCP, although the accuracy remained moderate. The PE based on preoperative corneal measurements was correlated to the amount of corneal flattening; the latter could be predicted by multiple linear regression accounting for anterior and posterior corneal radii (P = .0002) and was correlated to the preoperative anterior/posterior ratio. CONCLUSIONS: Constant optimization is beneficial for combined DMEK and phacoemulsification. Predicting postoperative corneal flattening may improve the results of IOL power accuracy. [J Refract Surg. 2022;38(7):435-442.].

Topical Corticosteroids and Fungal Keratitis: A Review of the Literature and Case Series.

The management of fungal keratitis is complex since signs and symptoms are subtle and ocular inflammation is minimal in the preliminary stages of infection. Initial misdiagnosis of the condition and consequent management of inflammation with corticosteroids is a frequent occurrence. Topical steroid use is considered to be a principal factor for development of fungal keratitis. In this review, we assess the studies that have reported outcomes of fungal keratitis in patients receiving steroids prior to diagnosis. We also assess the possible rebound effect present when steroids are abruptly discontinued and the clinical characteristics of three patients in this particular clinical scenario. Previous reports and the three clinical descriptions presented suggest that in fungal keratitis, discontinuing topical steroids can induce worsening of clinical signs. In these cases, we recommend to slowly taper steroids and continue or commence appropriate antifungal therapy.

Two-step keratoplasty for deep vascularized corneal opacity with severe peripheral thinning following Acanthamoeba keratitis.

PURPOSE: In cases of corneal opacity with vascularization and peripheral thinning, traditional keratoplasty techniques have several risks and drawbacks. We report the results of a two-step surgical strategy consisting in performing a large diameter tectonic lamellar keratoplasty (TLK) to restore appropriate corneal thickness and an avascular recipient bed, followed by central optical PK within the lamellar graft at a later date. METHODS: This single-institution study analyzes the results of 7 eyes of 7 patients who received PK after large diameter TLK. All patients were affected by deep post-infectious corneal opacity with persistent stromal vascularization and peripheral thinning. The main outcomes measured were graft survival, visual acuity, refraction, and endothelial cell density. RESULTS: TLK was performed in all cases with 10/10.1-mm diameters. After a mean interval of 14 months, central PK was performed with a median host-graft diameter of 7.75/8.25 mm. Mean follow-up after PK was 52 months. At last follow-up, 6/7 (86%) grafts were clear. Endothelial rejection occurred in 5/7 (71%) eyes, with one patient having multiple episodes and subsequent graft failure. At 2 years, all patients had a visual acuity ≥ 20/40, with an average refractive astigmatism of 3.75 diopters. CONCLUSION: Optical PK within a previous TLK is a safe and efficient technique for treating deep corneal opacity associated with extensive vascularization and peripheral thinning. Extended follow-up period is necessary to assess endothelial cell loss and long-term efficacy of the procedure.

Combined central retinal vein occlusion and branch retinal artery occlusion treated with intravitreal dexamethasone implant: A case report.

PURPOSE: To report a case of combined central retinal vein occlusion and branch retinal artery occlusion in a 51-year-old male with a very good response to dexamethasone implant therapy. METHODS: This is a descriptive case report based on data from clinical records, patient observation and follow-ups, and analysis of acquired diagnostic tests. RESULTS: A 51-year-old man presented with sudden vision loss and best-corrected visual acuity of 20/40 in his left eye. A pale inferotemporal arterial branch course area along with increased vascular tortuosity, retinal hemorrhages, optic disk swelling, and macular edema were observed on slit lamp biomicroscopy examination. Right eye was normal. Diagnosis of combined central retinal vein occlusion and branch retinal artery occlusion in left eye was confirmed by fluorescein angiography and color fundoscopy, respectively. Optical coherence tomography confirmed subretinal fluid and intraretinal cysts with a prominent middle-limiting membrane in the inner synaptic portion of the outer plexiform layer, corresponding to areas of paracentral acute middle maculopathy. Intravitreal dexamethasone implant was administered to the patient. One month later, visual acuity was recovered with complete absorption of macular edema. Functional and anatomical stabilization were confirmed after 24 months. CONCLUSION: Combined central retinal vein occlusion and branch retinal artery occlusion represents a rare condition, with variable functional outcomes due to the long-term complications such as macular edema. We hypothesize that prompt diagnosis and immediate intravitreal corticosteroid implant therapy reduced macular edema, thus contributing to arterial perfusion improvement, which in this case lead to a full sustainable recovery with limited functional and anatomical damage.

Corneal collagen cross-linking for management of keratoconus in patients affected by Tourette syndrome.

PURPOSE: To present a series of two patients affected by Tourette syndrome (TS) and progressive keratoconus. CASE SERIES: Two young male patients with keratoconus and TS were referred to our center. In both patients eye rubbing was present and in one patient, an ocular tic was present determining blepharospasm. Progression of keratoconus occurred in both cases and corneal collagen cross-linking (CXL) was performed. All treated eyes showed topographic stability with stable refraction and conserved visual acuity, with a follow-up period ranging from 1.5 to 2.5 years. CONCLUSION: Patients with keratoconus and TS should be observed frequently to document topographical and refractive changes, and in case of progressing disease, CXL should be performed in order to prevent further progression.

Comparison of two popular nuclear disassembly techniques for cataract surgeons in training: divide and conquer versus stop and chop.

PURPOSE: To compare two common phacoemulsification techniques in the learning curve phase, and their effect on ultrasound energy dissipation. METHODS: One hundred and ten consecutive patients scheduled for cataract surgery with the same surgeon in training were prospectively enrolled. Study was divided in two parts. In the first one, 60 patients were stratified for cataract grade [nuclear opalescence (NO) grade 2-4] and divided in two groups receiving surgery with the divide-and-conquer technique (Group-1) and with the stop-and-chop technique (Group-2). In the second part, 50 patients were stratified according to cataract grade (NO2-6), and the surgeon had to choose one of the two techniques according to personal preference. The primary outcome was the cumulative dissipated energy (CDE). RESULTS: Significant differences of CDE were observed between the NO3 and NO4 cataracts in Group-1. In Group-2, this difference was not significant, suggesting that with more advanced cataracts, the stop-and-chop technique allows less ultrasound use. In the second part of the study, the stop and chop was most frequently used for more advanced cataracts. When considering harder cataracts (NO5-NO6), patients receiving surgery with the divide-and-conquer technique had higher CDE values compared to stop and chop. CONCLUSIONS: Both divide-and-conquer and stop-and-chop techniques are efficient in the learning curve. Stop and chop dissipates less energy in harder nuclei. Once surgeons reach sufficient experience with both techniques, they should switch to a stop-and-chop technique, allowing lower levels of ultrasound energy.

Corneal collagen cross-linking in paediatric patients affected by keratoconus.

BACKGROUND/AIMS: To evaluate the effectiveness of corneal collagen cross-linking (CXL) in paediatric patients. METHODS: Fifty-two eyes of 43 paediatric patients with progressive keratoconus were enrolled in a prospective cohort study. Corneal CXL was performed using a conventional technique with instillation of 0.1% riboflavin solution containing dextran 20% for 30 min during the soaking phase and during the 30 min ultraviolet A irradiation (3 mW/cm2). Visual outcomes, topographic keratometry, maximum keratometry (K-max), refractive astigmatism, demarcation line and endothelial cell density were measured postoperatively. RESULTS: A significant decrease of K-max from 59.30±7.08 to 57.07±6.46 (p<0.001) was observed 2 years after treatment. Uncorrected visual acuity improved from 0.59±0.41 LogMAR (logarithm of the minimum angle resolution) to 0.46±0.33 LogMAR (p=0.06) 2 years after the procedure, while best spectacle corrected visual acuity improved from 0.17±0.11 LogMAR to 0.15±0.12 LogMAR (p=0.17). Twenty-five eyes had K-max values of 60 dioptres (D) or greater. In this subgroup, K-max significantly decreased from 64.94±4.99 D to 62.25±4.42 D at 2 years (p<0.001). The demarcation line of the CXL treatment had a mean value of 249±74 µm and did not show a significant correlation with K-max flattening (Spearman r=0.019, p=0.899). Endothelial cell density remained stable 2 years after the procedure, changing from 2800±363 to 2736±659 cells/mm2 (p=0.90). CONCLUSION: CXL is an effective treatment for avoiding keratoconus progression in paediatric patients. The procedure is safe and successful in stabilising keratoconus in eyes with more advanced forms of the disease, characterised by topographic K-max values greater than 60 D.