Transepithelial Accelerated Crosslinking for Progressive Keratoconus: A Critical Analysis of Medium-Term Treatment Outcomes.

Purpose: To report the 4-year outcomes of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) in the treatment of eyes with progressive keratoconus (KC). Methods: Eyes of patients who underwent TE-ACXL (6mW/cm2 for 15 minutes) for progressive KC and presented 48 months of follow-up were included. Corrected distance visual acuity (CDVA), keratometry measurements (Kmax, maximum keratometry, Kmean, mean keratometry and Astg, corneal astigmatism), thinnest corneal thickness (PachyMin), and topographic, and tomographic indices (specifically the posterior radius of curvature from the 3.0 mm centered on the thinnest point of the cornea (PRC), and the D-index) were analysed preoperatively and every 12 months after TE-ACXL, up to 48 months. Progression after TE-ACXL was considered when eyes presented ≥1 criteria: (1) increase of ≥1D in Kmax or increase of ≥0.75D in Kmean or increase of ≥1D in Astg; (2) reduction of ≥0.085 mm in PRC; (3) decrease ≥5% in PachyMin. Results: 41 eyes from 30 patients were included, with a mean age at crosslinking of 20.90±4.69 years. There was a significant increase in Kmean (+0.64±1.04 D, p<0.001; +0.98 ± 1.49 D, p<0.001; +1.27±2.01 D, p<0.001; +1.13±2.00 D, p=0.006) and a significant decrease in PRC throughout follow-up (-0.12±0.22, p=0.002; -0.15±0.24, p<0.001; -0.17±0.43, p=0.021; -0.16±0.43, p=0.027). PachyMin decreased significantly at 36 and 48 months (-8.50±15.93 µm, p=0.004; -7.82±18.37, p=0.033). According to our progression criteria, there was a major progression rate throughout follow-up (57.1%, 61.1%, 58.8%, and 67.9%, respectively). Surgery and follow-up were uneventful in all subjects. Eleven eyes (26.8%) required further procedures, ≥36 months after the initial TE-ACXL, due to persistent progressive disease. Conclusion: TE-ACXL proved to be a safe therapeutic option for progressive KC. However, its efficacy is deemed unsatisfactory, as a notable proportion of affected eyes may continue to advance within a 4-year timeframe, necessitating additional procedures to halt the disease's course.

Clinical outcomes and prognostic factors in Acanthamoeba keratitis.

PURPOSE: To report clinical findings and prognostic factors for visual and morphological outcomes in patients with Acanthamoeba keratitis (AK). METHODS: Single-center, retrospective, longitudinal study of 51 cases of AK diagnosed by real-time polymerase chain reaction (RT-PCR) between March 2010 and October 2022. The primary outcome was the final best corrected visual acuity (BCVA). Poor visual outcome was defined as a final BCVA ≥ 1 logMAR unit, while good visual outcome was defined as a final BCVA < 1 logMAR unit. Eyes from these two groups were compared, regarding demographic and initial clinical variables, anti-Acanthamoeba treatment used, and complications of the disease. Early diagnosis was defined as ≤ 14 days from symptom onset to diagnostic confirmation and initiation of Acanthamoeba medical treatment. Multivariable logistic regression was used to determine predictors of poor visual outcome. RESULTS: A total of 51 eyes from 46 patients diagnosed with AK, all contact lens (CL) wearers, were included in this study. Average follow-up was 39.0 ± 30.2 [total range 14-120] months. Thirty-one eyes (60.8 %) presented good visual outcome, with a lower baseline age (30.5 ± 9.0 vs. 42.3 ± 15.8; p = 0.020), better initial BCVA (0.8 ± 0.7 logMAR units vs. 1.3 ± 0.9 logMAR units; p = 0.047), higher rate of early diagnosis (45.2 % vs. 5.6 %; p = 0.004), and higher rate of therapeutic epithelial debridement (64.5 % vs. 10 %; p < 0.001). 20 eyes (39.2 %) presented poor visual outcome, with 12 eyes undergoing evisceration/enucleation (23.5 %). These 20 eyes presented a higher rate of complications (90 % vs. 61.3 %; p = 0.031). In multivariable analysis, early diagnosis of AK (OR 19.78; 95 % CI 2.07-189.11; p = 0.010) and therapeutic epithelial debridement (OR 19.02; 95 % CI 3.27-110.57; p = 0.001) were associated with a good visual outcome. CONCLUSIONS: In the present study, poor visual outcome was present in 39 % of affected eyes. Early AK diagnosis (≤14 days from symptom onset) and therapeutic epithelial debridement were associated with good final visual outcome.

Microbiological Profile of Infectious Keratitis During Covid-19 Pandemic.

Purpose: The Covid-19 pandemic introduced significant changes in our daily life, including the widespread use of face masks. The purpose of this study was to assess if significant changes occurred in the microbiological profile of infectious keratitis. Patients and Methods: A retrospective study was performed, based on a survey review of the electronic medical records of all patients with presumed infectious keratitis, between March 2020 and October 2021. The microbiological isolates in this sample (pandemic group) were compared with those obtained in our center between 2009 and 2018 (pre-pandemic group). Results: A total of 194 samples were included in the pandemic group. We obtained a culture-positivity rate of 43.3%, which was significantly higher when compared with the pre-pandemic data (35.15%, p = 0.033). Several further significant differences were found between the pandemic and the pre-pandemic groups: the proportion of bacteria, including gram-positive and gram-negative groups, was higher in our sample (pre-pandemic vs pandemic: 76.78% vs 83.33%, p = 0.010; 53.35% vs 60.71%, p = 0.016; 23.43% vs 34.52%, p = 0.005, respectively); two populations of Gram-positive bacteria found in this study were not isolated in the pre-pandemic sample - Dolosigranulum pigrum and Propionibacterium spp.; and two bacterial isolates were significantly increased in our sample - Corynebacterium spp. (18.41% vs 29.76%, p = 0.003) and Pseudomonas aeruginosa (9.00% vs 16.66%, p = 0.012). Conclusion: In conclusion, significant changes were found in the microbiological profile of infectious keratitis in our center during the Covid-19 pandemic. While these changes could be related to face mask use, more observational and experimental studies are needed to explore this possible association.

Best Fit Sphere Back and Adjusted Maximum Elevation of Corneal Back Surface as Novel Predictors of Keratoconus Progression.

Purpose: We evaluated the Maximum Elevation of Corneal Back Surface adjusted to the same Best Fit Sphere Back (BFSB) between timeline measurements (AdjEleBmax) and the BFSB radius (BFSBR) itself as new tomographic parameters for documentation of ectasia progression and compare them with the most recent and reliable parameters used on keratoconus (KC) progression. Results: We evaluated the performance and the ideal cutoff point of Kmax, D-index, posterior radius of curvature from the 3.0 mm centered on the thinnest point (PRC), EleBmax, BFSBR, and AdjEleBmax as isolated parameters to document KC progression (defined as a significant change in two or more variables), we found a sensitivity of 70%, 82%, 79%, 65%, 51%, and 63% and a specificity of 91%, 98%, 80%, 73%, 80%, and 84% to detect KC progression. The area under the curve (AUC) for each variable was 0.822, 0.927, 0.844, 0.690, 0.695, 0.754, respectively. Conclusion: AdjEleBmax presented a greater specificity, larger AUC, and better performance compared to EleBmax without any adjustment, with similar sensitivity. Although AdjEleBmax and BFSB demonstrated smaller AUC and specificities comparing with Kmax and D-Index, AdjEleBmax still presented a good performance with a reasonable AUC. Since the shape of the posterior surface, more aspheric and curved than the anterior, may facilitate detection of change, we suggest the inclusion of AdjEleBmax in the evaluation of KC progression in conjunction with other variables to increase the reliability of our clinical evaluation and early detection of progression.

Keratoconus enlargement as a predictor of keratoconus progression.

Numerous approaches have been designated to document progression in keratoconus, nevertheless there is no consistent or clear definition of ectasia progression. In this present study, we aim to evaluate Keratoconus Enlargement (KCE) as a parameter to document ectasia progression. We define KCE as an increase of more than 1D in the anterior curvature of non-apical corneal areas. We have designed a longitudinal study in 113 keratoconic eyes to assess keratoconus progression. KCE was compared with variables commonly used for detection of keratoconus progression like Kmax, Km, K2, PachyMin, D-Index, Corneal Astigmatism and PRC of 3.0 mm centered on the thinnest point. The variations of keratometric readings, D-index and ELEBmax showed positive associations with KCE. Evaluating the performance of Kmax, D-index and KCE as isolated parameters to document keratoconus progression we found a sensitivity of 49%, 82% and 77% and a specificity of 100%, 95% and 66% to detect keratoconus progression (p < 0.001 for all). This difference in sensitivity can be explained by the changes in keratoconus outside the small area represented by Kmax. The inclusion of KCE should be considered in the evaluation of keratoconus progression in conjunction with other variables to increase the reliability of our clinical evaluation.

A 10-Year Retrospective Clinical Analysis of Fungal Keratitis in a Portuguese Tertiary Centre.

PURPOSE: To determine the microbiological profile, risk factors, treatment and surgical intervention rates of fungal keratitis at a tertiary referral centre. METHODS: A retrospective review of microbiological and medical records from hospitalised patients treated for fungal keratitis at Centro Hospitalar Universitário de São João from 2009 to 2019 was conducted. RESULTS: Overall, 43 patients were included in our study. The mean age of patients was 63.7 years and 46.5% were men. In culture were isolated 22 (51.2%) filamentous fungi and 21 (48.8%) yeast. Candida species (n = 20, 46.5%), Fusarium species (n = 10, 23.4%) and Aspergillus species (n = 4, 9.3%) were the most common isolated species. Important risk factors were contact lens use (n = 24, 55.8%), long-term users of topical corticosteroids (n = 19, 44.2%) and previous keratitis (n = 19, 44.2%). Yeast isolates had a statistically significant higher prevalence in long-term users of topical corticosteroids compared to filamentous ones (p = 0.043). Twenty-four cases (55.8%) required surgical intervention, of which 23 cases underwent therapeutic penetrating keratoplasty. Ocular complications, such as evisceration was noted in 12 patients (27.9%) and endophthalmitis in 5 (11.6%). No statistically significant changes of best corrected visual acuity (BCVA) were found after treatment (p = 0.687). CONCLUSION: Most patients with fungal keratitis have associated risk factors. Filamentous and yeast species have equally prevalent etiologies. In general, our results mirror how difficult and challenging the approach and treatment of fungal keratitis could be.

Increased choroidal thickness is not a disease progression marker in keratoconus.

The recent findings of increased Choroidal Thickness (CT) in Keratoconus (KC) patients raised the question of whether CT could be an indicator of progressive KC. To test this hypothesis, we evaluated and compared the choroidal profile in progressive and non-progressive KC. We ran a cross-sectional observational study in 76 patients diagnosed with KC, age 14-30, to assess KC progression. Progression was defined as when at least two of the studied variables confirmed progression (Kmax, Km, PachyMin, D-Index, Astig, K2, 3 mm PCR). Included patients performed a Spectralis Optical Coherence Tomography (OCT) with enhanced depth image (EDI) technology to evaluate choroidal profile. Choroidal measurements were taken subfoveally and at 500 µm intervals from the fovea, in 7 different locations, and compared between groups. Multivariate linear regression analyses were also performed to assess the influence of CT in KC progression. Thirty-six eyes (47.4%) were classified as KC progressors. The mean subfoveal CT observed in the total sample was 382.0 (± 97.0) µm. The comparison between groups (progressive and non-progressive KC) showed no differences in the locations evaluated (mean subfoveal CT difference between groups was 2.4 µm, p = 0.915). In the multivariate analysis CT seems not be influenced by KC progression (B = 6.72 µm, 95% CI - 40.09 to 53.53, p = 0.775). Assessment of choroidal profile does not appear to be a useful tool to differentiate progressive and non-progressive KC. Further research is needed in order to better understand the role of choroid in KC.

Transepithelial Accelerated Corneal Collagen Cross-Linking: Two-Year Results.

PURPOSE: To report 2-year outcomes of trans-epithelial accelerated corneal collagen crosslinking (TE-ACXL) procedure in the treatment of progressive keratoconus patients. PATIENTS AND METHODS: Twenty-four eyes from 24 patients who underwent TE-ACXL (6mW/cm2 for 15 minutes) were included in this retrospective interventional study. Best-corrected visual acuity (BCVA), keratometry values, thinnest corneal thickness (PachyMin) and topometric indexes were analysed preoperatively and at 6-month, 12-month, 18-month and 24-month postoperative. Progression was assessed by increase ≥1.00D in maximum keratometry (Kmax); increase ≥1.00D in corneal astigmatism; decrease ≥2% in PachyMin; increase ≥0.42 in D-index. RESULTS: There were no complications during or after TE-ACXL. No significant differences (Δ) were observed between baseline and 12-month or 24-month postoperative: ∆BCVA (-0.08 ± 0.25, p=0.190; -0.04 ± 0.17, p=0.588), ∆Kmax (-0.08 ± 1.32, p=0.792; -1.04 ± 1.89, p=0.135), ∆Astigmatism (-0.15 ± 0.89, p=0.485; -0.24 ± 1.38, p=0.609), ∆PachyMin (-0.56 ± 15.70, p=0.882; 0.56 ± 18.74, p=0.931), ∆Index Surface Variation (∆ISV) (-2.11 ± 10.27, p=0.395; -4.67 ± 17.32, p=0.442), ∆Index Vertical Asymmetry (∆IVA) (-0.05 ± 0.17, p=0.208; -0.08 ± 0.26, p=0.397), ∆Index Height Decentration (∆IHD) (0.00 ± 0.02, p=0.368; -0.01 ± 0.04, p=0.484), ∆KI (0.00 ± 0.05, p=0.851; 0.01 ± 0.06, p=0.877) and ∆D-index (0.15 ± 1.14, p=0.572; 0.06 ± 1.36, p=0.892). Eleven to 33% of patients had disease progression at 24-month postoperative according to the parameters used to determine progression. CONCLUSION: Although some patients maintain disease progression, TE-ACXL seems to be a safe and effective treatment for keratoconus over the 2-year follow-up period. Studies with longer follow-up periods and larger patient cohorts are recommended.

Increased Choroidal Thickness in Keratoconus Patients: Perspectives in the Disease Pathophysiology.

PURPOSE: To analyze and compare choroidal thickness between keratoconus (KC) patients and age-matched non-KC subjects. METHODS: A cross-sectional, case-control study. One hundred and thirty-four keratoconic eyes and 78 control eyes, from individuals aged from 12 to 30 years old, were studied. Patients with KC followed in Corneal Department of Centro Hospitalar São João, Porto, Portugal, were identified and consecutively included between December 2017 and February 2018. A spectral-domain optical coherence tomography (OCT) using depth enhanced imaging was performed, and choroidal thickness in the center of the fovea and at 500 µm intervals along a horizontal section was measured and compared. RESULTS: The statistical analysis showed that keratoconic eyes present a thicker choroid in every measured location (p < 0.05). Mean subfoveal choroidal thickness (SFCT) values obtained were 375.86 ± 89.29 and 322.91 ± 85.14 in keratoconus and control groups, respectively (p < 0.001). In a multivariate analysis, SFCT was significantly associated with spherical equivalent (p=0.004) and the presence of keratoconus (p < 0.001), but not with age (p=0.167), gender (p=0.579), or best-corrected visual acuity (p=0.178). In a "fixed model," keratoconus patients were found to have a 67.55 µm (95% CI 36.61-98.49) thicker subfoveal choroid compared to controls. CONCLUSION: Keratoconus patients seem to have a thicker choroid than healthy individuals. The exact pathophysiological mechanism resulting in a thicker choroid in KC patients is not known, but it could possibly be associated with inflammatory choroidal mechanisms.

Microbiological Profile of Infectious Keratitis in a Portuguese Tertiary Centre.

The microbiological profile of infectious keratitis has shown great differences across the world. Due to the continuous shifting trends in microbiological profile and antibiotic resistance patterns reported in several studies, constant local updates are crucial to provide an adequate treatment. The propose of this study was to analyze the incidence of infectious keratitis, possible changing trends in microbiological profile, and bacteria sensitivity to commonly used antibiotics, in our tertiary center, in the last 10 years. A retrospective study was performed, based on the survey review of electronic medical records of all patients with presumed infectious keratitis, between January 1, 2009, and December 31, 2018. Microbial cultures were performed, and patients were treated according to an internal protocol. A total of 1360 samples were included. We obtained a 35.1% culture-positive rate. Bacteria accounted for 76.78% of all positive scrapes (53.34% were Gram positive and 23.44% were Gram negative), Acanthamoeba for 12.13%, fungi for 8.16%, and virus for 2.93%. The most frequent agent identified was Corynebacterium macginleyi (18.41%), followed by Staphylococcus aureus (17.78%), Streptococcus pneumoniae (9.41%), and Pseudomonas aeruginosa (9.00%). We identified at least one ophthalmologic risk factor in 410 patients (85.77%). Trauma and contact lens wear were the most common risk factors found, accounting for 34.94% (n = 167) and 33.47% (n = 160) of cases. Sensitivity to fluoroquinolones and aminoglycosides was tested in all bacterial isolates, presenting values of 96.66% and 98.12%. In our region, the most common bacteria are Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa, and they showed high sensitivity rates to first-line antibiotics, without any modification or emergence of antibiotic resistance trends during the 10 years of the study. For this reason, we decided to maintain the same internal protocol in our tertiary centre.

Transepithelial accelerated versus conventional corneal collagen crosslinking in patients with keratoconus: a comparative study.

PURPOSE: To systematically compare the efficacy of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) with conventional corneal collagen crosslinking (C-CXL) in patients with progressive keratoconus. METHODS: Eyes of patients with progressive keratoconus who were treated with C-CXL (3 mW/cm2 for 30 minutes) were compared with those who underwent TE-ACXL (6 mW/cm2 for 15 minutes). Best-corrected visual acuity (BCVA), keratometry values, corneal thickness, and topometric indexes were compared before CXL, and at 2 months, 6 months, and 12 months postoperatively. RESULTS: The study enrolled 26 eyes of which 16 had TE-ACXL and 10 had C-CXL. Both groups were comparable at baseline and 12 months in terms of BCVA (P=0.16 and P=0.57), Kmax (maximum keratometry) (P=0.31 and P=0.73), pachymetry (P=0.75 and P=0.37), index of surface variance (ISV) (P=0.45 and P=0.86), index of vertical asymmetry (IVA) (P=0.26 and P=0.61), and index of height decentration (IHD) (P=0.27 and P=0.86, respectively). We did not observe significant differences between preoperative and 12-month postoperative readings in within-group analysis: ΔKmax (TE-ACXL, -2.13±5.41, P=0.25 vs C-CXL, 0.78±1.65, P=0.17), Δpachymetry (TE-ACXL, 4.10±14.83, P=0.41 vs C-CXL, -8.90±22.09, P=0.24), ΔISV (TE-ACXL, -8.50±21.26, P=0.24 vs C-CXL, 3.80±12.43, P=0.36), ΔIVA (TE-ACXL, -0.12±0.31, P=0.26 vs C-CXL, 0.03±0.18, P=0.61), and ΔIHD (TE-ACXL, -0.03±0.07, P=0.18 vs C-CXL, -0.01±0.03, P=0.88). CONCLUSION: Both TE-ACXL and C-CXL were similarly effective. Further follow-up is required to determine whether these techniques are comparable in the long-term.

Clinical and Microbiological Profile of Bacterial Microbial Keratitis in a Portuguese Tertiary Referral Center-Where Are We in 2015?

OBJECTIVES: To study the microbial profile, antibiotic susceptibility pattern, risk factors, therapeutic trends, and clinical outcomes for microbial keratitis (MK) in a tertiary health care center. METHODS: All cases with suspected bacterial keratitis that were followed at consultation from September 2007 to August 2015 were included. Microbial cultures were obtained and patients were managed following an internal protocol. RESULTS: Two hundred thirty-five patients were included, with a mean age of 50.01±20.73 years. We obtained a 38.4% culture-positive rate, with higher proportion of gram-positives (70.8%). The commonest agents were Staphylococcus aureus (23.1%), Corynebacterium macginleyi (20.0%), and Pseudomonas aeruginosa (13.8%). Fluoroquinolone susceptibility was 97%, with no trend toward its decrease. A total of 95.7% had local risk factors, being trauma and contact lens wear the most common (28.9% each), with different age and pathogens distributions (P<0.001). Topical fluoroquinolones were first-line treatment in 99%, in association with aminoglycosides in 81.6%. Good initial response was registered in 95.9%, but 4.1% needed to step up treatment to fortified antibiotics, mainly if Pseudomonas (P=0.021). Good outcome was achieved in 81.8%, negatively affected by exposure and herpetic keratitis (P<0.001), central location (P=0.01), presence of Tyndall (P<0.001), corneal edema (P<0.001), and worse initial best-corrected visual acuity (P<0.001), but not Pseudomonas isolate (P=0.724). CONCLUSIONS: Gram-positives are the most frequent pathogens and shifting trends in the isolate distribution or emergence of resistant strains were not demonstrated. The susceptibility to first-line antibiotic agents remained high. We suggest a more aggressive approach to P. aeruginosa cases or MK presenting with poor outcome variables.

Beauveria bassiana keratitis in bullous keratopathy: antifungal sensitivity testing and management.

PURPOSE: Beauveria bassiana is a ubiquitous fungus available as an insecticide. In humans, it has limited virulence; to our knowledge, only 3 cases of invasive disease and 10 cases of keratitis have been documented. METHODS AND RESULTS: We report the first case of B bassiana keratitis in a patient with aphakic bullous keratopathy. The fungal keratitis proved to be highly resistant to topical clotrimazole. Molecular identification was based on DNA sequence analysis. The minimal inhibitory concentrations (MIC) obtained were 2 µg/mL for voriconazole, 0.250 µg/mL for posaconazole, and >128 µg/mL for fluconazole; amphotericin B MIC was >16 µg/mL. In the absence of clinical improvement, a penetrating keratoplasty (PK) was performed. The patient was discharged on topical and systemic voriconazole and prednisolone 40 mg PO/day. The eye remained calm with a transparent cornea and clear anterior chamber. CONCLUSIONS: B bassiana keratitis is extremely rare, with only a few cases reported. Its risk factors are unknown. We report the first case in a patient with aphakic bullous keratopathy, which proved highly resistant to antifungal therapy (antifungal susceptibility results are presented). A PK was necessary for clinical improvement. A review of the literature is performed in an effort to define therapeutic strategies.