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Purpose: To analyse the temperature of the corneal surface in keratoconus during corneal customized crosslinking (CXL) with a preserved epithelium (epi-on) under oxygen flow, and epi-off CXL in room air, and to assess the effect of pre-heating the oxygen., Methods: This masked, intra-individual comparing randomized study included 14 participants with bilateral progressive keratoconus treated with bilateral CXL: one eye with epi-on CXL under a flow of 2.5 L/min oxygen; the fellow eye with epi-off CXL in room air. In a second setting involving 12 healthy participants, room-tempered oxygen was flushed over one eye and oxygen pre-heated to 37°C over the fellow eye. The corneal surface temperature was assessed with infrared photography., Results: A reduction in corneal surface temperature was seen from the pre-treatment application of topical riboflavin in the epi-off group (-1.1 ± 1.0°C, p < 0.001). The temperature increased during the first half of the CXL treatment in both groups (+0.7 ± 1.2°C, p = 0.041 for epi-on; +0.7 ± 0.9°C, p = 0.023 for epi-off CXL, respectively). In epi-on CXL an overall temperature increase was seen during the treatment (+0.8 ± 1.2°C, p = 0.016). In the second setting, pre-heating the oxygen rendered a surface temperature increase of +1.8 ± 0.2°C (p < 0.001)., Conclusion: In epi-off CXL, the application of topical room-tempered riboflavin decreases the corneal surface temperature, likely due to increased evaporation. A slight temperature increase is seen during CXL with both epi-on and epi-off CXL, albeit far below the corneal safety limit. The corneal temperature can, however, be increased by applying pre-heated oxygen, a possible approach to modify or augment the treatment effect in CXL., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Methyl aminolevulinate (MAL) photodynamic therapy (PDT) is commonly used for field treatment of actinic keratoses (AKs). In standard natural daylight PDT (n-DL-PDT) the first step, after the application of chemical solar filter, is removal of crusts and scales by curettage, followed by the application of MAL cream. Some patients experience intense pain during curettage and stinging after application of the photosensitizer to just curettaged skin., Objectives: To evaluate whether n-DL-PDT without curettage, but preceded by application of keratolytics, would maintain a similar efficacy, based on clinical, dermoscopic, reflectance confocal microscopy (RCM) assessments, safety and patient satisfaction as standard n-DL-PDT with curettage., Methods: Forty patients with multiple AKs on the face and/or scalp were enrolled in this study. Patients were randomized into two groups of treatment as follows: (i) MAL n-DL-PDT without previous curettage, preceded by skin preparation at home with keratolytics (30% urea cream, twice a day for 7 days; -Cur group) and (ii) MAL n-DL-PDT preceded by skin preparation at the hospital with curettage (+Cur group)., Results: Thirty-nine participants completed the study. Four hundred and twenty-one AKs in -Cur group and 337 AKs in +Cur group were treated. The mean reduction in the number of AK lesions 3 months after the treatment was 10.7 (-54.7%) in the -Cur and 10.4 (-58.7%) in the +Cur group. We found that the differences in terms of efficacy and patient satisfaction comparing the two treatment regimens were not statistically significant. The pain score reported during and after daylight exposure was similar and low in both groups. Moreover, no unexpected adverse events occurred during the trial period., Conclusions: According to our results, curettage is not necessary to obtain the full treatment effect of n-DL-PDT. We experienced in a real-life setting that n-DL-PDT protocol could be changed by replacing curettage with keratolytics., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose: To evaluate the relationship between subjective (slit lamp examination [SLE]) and objective (densitometry) measurements of corneal haze after accelerated corneal crosslinking (aCXL), assess the relationship between densitometry and corrected distance visual acuity (CDVA), and determine the effect of baseline characteristics on densitometry after aCXL in eyes with progressive keratoconus and other ectasias., Setting: Kensington Eye Institute and Bochner Eye Institute, Toronto, Canada., Design: Retrospective analysis of a prospective interventional cohort study., Methods: Scheimpflug-derived corneal densitometry, CDVA, maximum keratometry (K max ), and central corneal thickness were measured preoperatively and up to 1 year after aCXL, and post-operative haze was estimated with SLE (n = 483 eyes). A random effect model was used to examine the relationship between post-operative subjective haze with SLE and densitometry. Linear mixed models were used to examine the relationship between densitometry, pre-operative baseline characteristics, and CDVA., Results: There was a significant association between subjective haze with SLE and densitometry (p < 0.001). There was a significant relationship between CDVA and densitometry: for every 10 GSUs of increased densitometry in the 0-2 mm zone, CDVA worsened by approximately half a Snellen line (p < 0.001). Age and pre-operative K max were significant predictors of densitometry. For every 10 years of age, densitometry increased by 0.68 GSUs (95% CI [0.27 to 1.07], p < 0.001). For every 10 D of increased preoperative K max , densitometry increased by 0.69 GSUs (95% CI [0.41 to 0.98], p < 0.001)., Conclusions: Subjective haze after aCXL estimated with SLE, is significantly associated with densitometry. Increased densitometry after aCXL is associated with a reduction in CDVA., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor., Objectives: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease)., Methods: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK., Results: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT., Conclusion: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h., (© 2023 European Academy of Dermatology and Venereology.)

Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate clinical practice in the diagnosis and treatment of progressive keratoconus with corneal crosslinking (CXL) in four Nordic countries., Methods: A questionnaire was sent to all centres at which keratoconus patients are evaluated and CXL is performed in Sweden, Denmark, Norway and Iceland. Nineteen of 20 centres participated., Results: CXL is performed approximately 1300 times per year in these four Nordic countries with a population of around 21.7 million (2019). In most cases, progression is evaluated using the Pentacam HR, and the maximum keratometry reading (K max ) is considered the most important parameter. The most frequently used treatment protocol in Scandinavia is the 9 mW/cm 2 epi-off protocol, using hydroxylpropyl methylcellulose riboflavin (HPMC-riboflavin). The participants deemed the following areas to be in most need of improvement: adaptation of the CXL protocol to individual patients (5/19), the development of effective epi-on treatment protocols (4/19), optimal performance of CXL in thin corneas (4/19), improvement of the definition of progression (2/19), and diagnosis of the need for re-treatment (2/19)., Conclusions: We concluded that the diagnosis of progressive keratoconus and the diagnostic equipment used are similar. Treatment strategies are also similar but are suitably different to provide an interesting basis for the comparison of treatment outcomes. The high degree of participation in this survey indicates the possibility of future scientific collaboration on CXL focusing on the areas deemed to need improvement. It would also be of interest to evaluate the possibility of creating a Nordic CXL Registry. The high number of CXL treatments performed ensures sufficient statistical power to solve many questions. Such a registry could be an important contribution to evidence-based care and would allow for longitudinal evaluation., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: Since July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first-choice treatment or regarded as a major treatment option., Materials and Methods: A questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage., Results: Our questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries., Conclusion: The shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public-private partnerships., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is highly efficacious for the treatment of nonhyperkeratotic actinic keratosis (AK), even when partially performed at home. To evaluate the long-term effectiveness, safety, and patient-reported outcomes of MAL DL-PDT performed completely by the patient in real life conditions. An open prospective study was conducted in Spain among patients diagnosed with at least five AK lesions on the face or the scalp. Patients received instruction and information in infographic format to perform MAL DL-PDT at home. All had been treated with 30% urea daily for 7 days before the day of MAL DL-PDT. Meteorological conditions on the day of the treatment and adverse effects were recorded. Patients underwent follow-up, and a second session of home-based MAL DL-PDT if deemed necessary, 3, 6, and 12 months after the initial treatment session. The study population consisted of 22 patients (19 men and three women, mean [standard deviation, SD] age, 72.05 [6.96] years). A complete response was observed in 47.7% of AK lesions at 3 months (p < 0.001) and 65.9% (n = 199) at 12 months (p < 0.001). Olsen grade II lesions showed the highest rate of response (76.07% at 12 months). The mean (SD) actinic keratosis area and severity index score decreased significantly from 4.99 (2.43) at baseline to 2.33 (1.01) at 12 months (p = 0.0234). Adverse effects were mild and expected. A majority of patients were "satisfied" or "very satisfied" with the treatment instruction provided (90.9%) and the treatment outcome (72.7%). MAL DL-PDT can be applied at home like any other topical treatment for AK. Our results indicate good long-term effectiveness, a high level of patient satisfaction, and no significant side effects., (© 2022 The Authors. Dermatologic Therapy published by Wiley Periodicals LLC.)

Photodynamic therapy (PDT) is an effective treatment for some non-melanoma skin cancers (NMSC) and actinic keratosis. To compare recurrence-free survival (RFS) rates between surgery alone and surgery with postoperative PDT in patients with NMSC in China. This retrospective cohort study included patients with pathologically confirmed NMSC or actinic keratosis treated by surgical excision with/without PDT. A total of 125 patients were included, including 72 patients (43 females) aged 57-75 years in the surgery alone group and 53 patients (32 females) aged 61-76 years in the surgery+PDT group. The most common NMSC types were squamous cell carcinoma and basal cell carcinoma, the most common lesion site was the head and neck, and the vast majority of patients had a primary disease and solitary lesions. There were no significant differences between groups in baseline characteristics. RFS rates in the surgery alone and surgery+PDT groups were, respectively, 100.0% and 98.1% at 1 week, 98.6% and 98.1% at 4 weeks, 97.2% and 98.1% at 8 weeks, 97.2% and 98.1% at 12 weeks, and 90.3% and 90.4% at 24 weeks, with no significant differences between groups. Adjuvant PDT after surgical excision of NMSC or actinic keratosis does not provide short-term improvement in RFS, but the results need to be confirmed by a formal randomized controlled trial., (© 2022 Wiley Periodicals LLC.)

Purpose: To determine corneal cross-linking (CXL) efficacy and chromophore penetration after excimer laser-assisted patterned de-epithelialization., Methods: Two-hundred-twenty porcine eyes were de-epithelialized ex vivo, either fully (mechanical; n = 88) or patterned (excimer laser; n = 132). Consecutively, corneas were impregnated with hypo- or hyperosmolar riboflavin (RF; n = 20, RF-D; n = 40, respectively) or water-soluble taurine (WST11; n = 40, and WST-D; n = 40, respectively), or kept unimpregnated (n = 80). Sixty corneas were subsequently irradiated, inducing CXL, with paired contralateral eyes serving as controls. Outcome measurements included strip extensiometry to assess CXL efficacy, and spectrophotometry and fluorescence microscopy to determine stromal chromophore penetration., Results: All tested chromophores induced significant CXL (p < 0.001), ranging from 7.6% to 14.6%, with similar stiffening for all formulations (p = 0.60) and both de-epithelialization methods (p = 0.56). Light transmittance was significantly lower (p < 0.001) after full compared with patterned de-epithelialization. Stromal chromophore penetration was comparable between fully and patterned de-epithelialized samples, with full penetration in RD and RF-D samples and penetration depths measuring 591.7 ± 42.8 µm and 592.9 ± 63.5 µm for WST11 (p = 0.963) and 504.2 ± 43.2 µm and 488.8 ± 93.1 µm for WST-D (p = 0.669), respectively., Conclusions: Excimer laser-assisted patterned de-epithelialization allows for effective CXL. Stromal chromophore concentration is, however, reduced, which may have safety implications given the need for sufficient UVA attenuation in RF/UVA CXL. The different safety profile of near-infrared (NIR) may allow safe WST11/NIR CXL even with reduced stromal chromophore concentration values. In vivo studies are needed to evaluate the benefits and further assess safety of excimer laser-assisted patterned de-epithelialization for corneal CXL., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or half-dose photodynamic therapy (PDT)., Methods: We retrospectively obtained optical coherence tomography (OCT) scans from a subset of patients from a randomized controlled trial on treatment-naïve eyes with cCSC allocated to either HSML treatment or half-dose PDT. OCT scans were evaluated prior to treatment and 6-8 weeks post-treatment, where we measured maximum SRF height and width, calculated the maximum height-to-maximum width-ratio (maxHWR) and calculated the total SRF volume., Results: Forty-one eyes of 39 cCSC patients were included. SRF morphology ranged from flat to dome-shaped, quantified as maxHWR ranging between 0.02 and 0.12. SRF volume was median 0.373 μl (range: 0.010-4.425 μl) and did not correlate to maxHWR (rho = -0.004, p = 0.982). Half-dose PDT was superior to HSML treatment in complete SRF resolution (RR = 3.28, p = 0.003) and in morphological changes of SRF (Δ maximum height , p = 0.001; Δ maximum width , p < 0.001; Δ volume , p = 0.025). SRF resolved completely in 19/22 PDT-treated eyes (86%) and 5/19 HSML-treated eyes (26%). SRF volume increased in five eyes (26%) after HSML treatment, and in none of the eyes after half-dose PDT. SRF morphology at baseline did not predict treatment outcomes., Conclusion: SRF morphology changed after both HSML treatment and half-dose PDT in cCSC, with SRF disappearing in most PDT-treated patients, whereas SRF volume increased in a sizeable proportion of HSML-treated patients. Baseline SRF characteristics measured in this study were unable to predict outcomes after either HSML treatment or half-dose PDT., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved., (© 2021 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Hemoporfin-mediated photodynamic therapy (HMME-PDT) is a vascular-targeted treatment for port-wine stains (PWS). However, the efficacy of this has varied and is difficult to predict. The objective of this study was to evaluate the efficacy of influential factors associated with HMME-PDT and provide a suitable method for predicting the efficacy. Patients with facial PWS who underwent HMME-PDT were retrospective analyzed. A total of 212 patients (93 males) with mean age of 13.01 ± 12.67 years (range, 1-51) years were included. There were 143 cases with red, 56 cases with purple, and 13 cases with hypertrophic-type PWS. The number of HMME-PDT sessions ranged 1-6. The excellent response rate after 1-4 PDT sessions was 9.4%, 17.6%, 32.7%, and 42.9%, respectively. The number of PDT treatments is associated with efficacy, and patients who underwent treatment with more than three sessions had response better than those who underwent treatment with less than three sessions (p = 0.003). Response to HMME-PDT in patients of different ages, previous treatment history, lip involvement, and vessels morphology showed significant differences after two treatment sessions (p = 0.001, 0.03, 0.014, and 0.001, respectively), while patients of different sex, subtype, lesion size, location (medial, lateral, or mixed), or non-vascular morphology showed no significant differences. Logistic regression analysis confirmed that the patients with lip hypertrophy (p = 0.002), history of more than five times prior treatment (p = 0.003), fewer PDT sessions (<3) (p = 0.000002), linear vessels (p = 0.007), and reticular vessels (p = 0.0003) showed association with poor response of HMME-PDT. In conclusion, HMME-PDT is an effective treatment for PWS. Patients who had underwent treatment for more than five times prior, lip hypertrophy, and linear vessels or reticular vessels under dermoscope showed association with poor efficacy., (© 2021 Japanese Dermatological Association.)

Purpose: To describe the treatment outcomes and recurrence risk of chronic central serous chorioretinopathy (cCSC) in patients who had complete resolution of subretinal fluid (SRF) after either primary half-dose photodynamic therapy (PDT) or high-density subthreshold micropulse laser (HSML) in the PLACE trial., Methods: This multicentre prospective follow-up study evaluated cCSC patients at 1 year after completion of the PLACE trial. Outcomes included: complete resolution of SRF on OCT, best-corrected visual acuity (BCVA) in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, retinal sensitivity on microperimetry and a visual function questionnaire (NEI-VFQ25)., Results: Twenty-nine out of 37 patients who received half-dose PDT and 15 out of 17 patients who received HSML could be evaluated at final visit. At final visit, 93% of the patients treated with half-dose PDT had complete resolution of SRF, compared with 53% of HSML-treated patients (p = 0.006). At final visit, the mean estimate increase in the PDT group compared with the HSML group was + 2.1 ETDRS letters, +0.15 dB for the retinal sensitivity and + 5.1 NEI-VFQ25 points (p = 0.103, p = 0.784 and p = 0.071, respectively). The mean estimated central retinal thickness in the half-dose PDT group was -7.0 µm compared with the HSML group (p = 0.566). The mean estimated subfoveal choroidal thickness in the half-dose PDT group was -16.6 µm compared with the HSML group (p = 0.359)., Conclusion: At 20 months after treatment, cCSC patients successfully treated with half-dose PDT are less likely to have recurrences of SRF compared with those successfully treated with HSML. However, functional outcomes did not differ., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate long-term results of photodynamic therapy (PDT) as a rescue treatment in patients with type 1 neovascularization refractory to intravitreal anti-vascular endothelial growth factor (VEGF)., Methods: Patients who underwent reduced-fluence PDT for refractory type 1 neovascularization, which showed persistent subretinal and/or intraretinal fluid after three or more consecutive anti-VEGF treatments, and were followed up for ≥24 months were reviewed., Results: Seventy-eight eyes of 78 patients were included, and 37 (47%) were classified as polypoidal choroidal vasculopathy (PCV). The mean number of anti-VEGF injections before rescue PDT was 8.5 ± 5.4, and the mean follow-up period after rescue PDT was 74.0 ± 29.4 months. At 3 months after rescue PDT, exudation completely resolved in 55 (71%) patients and vision significantly improved (p = 0.021). Resolution of exudation was associated with choroidal vascular hyperpermeability [odds ratio (OR), 3.82; p = 0.031] and lower maximal height of pigment epithelial detachment (OR, 0.69; p = 0.018). In these patients, exudation recurred in 49 (89%) after mean period of 13.5 months. Vision significantly worsened at 24 months after rescue PDT, and thereafter, and the vision decrease was more prominent in patients with PCV. Rescue PDT could be repeated for recurrent or persistent exudation without increasing the risk of complications., Conclusion: In patients with type 1 neovascularization refractory to anti-VEGF, reduced-fluence PDT is an effective and safe rescue treatment. Therapeutic efficacy wore off during long-term follow-up, but rescue PDT may be repeated safely., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To assess the effect of two high-oxygen epi-on PiXL treatments for low-grade myopia., Methods: This prospective, randomized, intra-individually comparing, single-masked study included 23 healthy volunteers (46 eyes) aged 18-35 years with mild myopia, -0.75 to -2.50 D manifest refractive spherical equivalent (MRSE). One eye was randomized to a 4.0-mm homogenous treatment zone and the fellow eye to a 4.0-mm annular zone (16:40 min at 30 mW/cm 2 , fluence 15 J/cm 2 ). Uncorrected distance visual acuity (UDVA), MRSE, best spectacle-corrected visual acuity (BSCVA), Scheimpflug light scattering depths, mean keratometry (K mean ) and endothelial cell count (ECC) were assessed through 24 months., Results: Similar improvements in UDVA were seen for the homogeneous and annular protocols at 1 month: -0.52 (-0.59, -0.39) and -0.49 (-0.59, -0.39) logMAR, respectively (medians and interquartile ranges, IQR), p = 0.91, and MRSE: +1.0 D (0.94, 1.31) and +1.0 D (0.69, 1.25), p = 0.17. Light scattering depths were 496 (465, 527) and 349 (247, 378) µm, respectively, and the reduction in mean keratometry was -0.8 D (-1.1, -0.7) and 0 D (-0.1, 0.1), p < 0.001. The treatment effect remained stable throughout 24 months. At 1 week, the participants reported less ocular discomfort with the annular protocol. No reductions were seen in BSCVA or ECC. No adverse events were reported., Conclusion: PiXL can reduce low-grade myopia and improve uncorrected vision in healthy eyes. The initial ocular discomfort may be reduced with an annular treatment zone. Further studies are needed to optimize PiXL treatment parameters., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare the efficacy of implanting a single Keraring segment according to a novel Q-value-based nomogram (QN) to that of segment implantation according to the manufacturer's standard nomogram (SN), for keratoconus treatment., Methods: This was a prospective, randomized controlled trial of 104 patients (104 eyes) with Amsler-Krumeich grade 1 or 2 keratoconus, and type 1 or 2 cone asymmetry determined according to manufacturer's classification. They were randomly distributed into two groups: group A patients (n = 52) underwent Keraring implantation according to the SN, and group B patients (n = 52) underwent implantation of a single (210° arc-length) Keraring segment according to the QN. Both treatments were combined with accelerated transepithelial cross-linking, and follow-up was 6 months. Main outcome measures were preoperative and postoperative visual acuity, subjective refraction and corneal topography., Results: At postoperative month 6, group B exhibited statistically significantly higher values of mean uncorrected distance visual acuity (UDVA), sphere, K2, K-average, K-max and Q-anterior (p = 0.02, 0.01, 0.002, 0.001, 0.0001 and 0.03, respectively) compared to that of group A. However, group A exhibited better refractive cylindrical improvements (p = 0.04). In group A, we documented spontaneous extrusion of one Keraring segment., Conclusion: Single 210° arc-length segment implantation using our objective QN was more efficacious for keratoconus treatment than using the subjective SN. The nomograms were comparable when the Q-anterior value was >-1.00; however, the QN was superior to the SN when the Q-anterior value was ≤-1.00. The QN yielded greater postoperative UDVA and smoother corneal remodelling than did the SN for treatment of grade 1 and 2 keratoconic eyes., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Photodynamic therapy (PDT) is considered as a valid treatment option in various branches of dentistry. This systematic review aims to evaluate the usefulness of PDT for treatment of oral premalignant and malignant lesions., Methods: The MeSH terms "Photodynamic therapy" and "PDT," in combination with other terms, have been searched by three search engines (PubMed, ISI Web of Science, and the Cochrane Library), and a systematic review has been performed. The Population, Intervention, Comparison, Outcomes, and Study design (PICOS) has been applied as method to outline our study eligibility criteria. Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) has been performed too., Results: Initial results were 1513. Definitely, 27 studies met our selection criteria., Conclusions: Topical PDT is an easy to perform technique, well-tolerated treatment and it appears to be an effective method with encouraging achievements in the treatment of premalignant and malignant lesions of the soft tissues of the oral cavity; nevertheless more studies are required to integrate the up-to-date experience of this application., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To analyse the vision-related quality of life (vr-QoL) in stable and progressive keratoconus (KC) patients with a still good visual acuity., Methods: Combined prospective/cross-sectional study design. The Refractive Status and Vision Profile (RSVP) and the National Eye Institute Visual Functioning - 25 (NEI-25) questionnaire were used in 16 emmetropic, 32 myopic and 56 KC patients, whereby KC patients with a stable (n = 26) and patients with a progressive stage (n = 30) and some of them before and after corneal cross-linking (CXL; n = 10) were included. All patients had a DCVA in at least one eye of ≥0.7 (decimal chart)., Results: The analyses revealed a minor decline of the vr-QoL from emmetropes to myopes to early KC patients with a stable disease. Nonetheless, sociological subscales (i.e. 'social functioning', 'role difficulties' and 'dependency') did not display statistically significant differences comparing these groups. In progressive KC, we could demonstrate a statistically significant decline also of these sociological subscales, which did not improve after CXL., Conclusion: Due to a still high and almost unaffected vr-QoL in early KC patients and the distinct decline after progression without rehabilitation after CXL, a reconsideration of current strategies to perform CXL only after a progression is diagnosed should be re-evaluated., (© 2020 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Vascular targeted photodynamic therapy (PDT) is a novel and promising therapy for the treatment of port-wine stains (PWS). There has been little prior exploration to our knowledge of how the dermatological vascular pattern may predict the response to PDT., Objectives: To analyse whether the vascular pattern classifications of PWS by dermoscopy can predict the efficacy of PDT., Methods: This prospective cohort study included 163 patients with a clinical diagnosis of PWS who were treated twice with hemoporfin-mediated photodynamic therapy (HMME-PDT) at two-month intervals and followed up for 6 months. The vascular manifestations of dermoscopy with PWS were independently classified into 8 categories by 3 dermatologists. Images of the lesions were taken using VISIA, and the vascular patterns were imaged by dermoscopy by the same investigator. Images were captured before and after each treatment. The efficacy was evaluated with pre- and post-treatment VISIA images, and correlations between efficacy and vascular patterns were analysed by four dermatologists in a blinded and independent manner, between 10 January 2019 and 11 December 2019., Results: In the dermoscopy images for the whole cohort, dotted and globular vessels (15.3%), short clubbed vessels (18.4%) and curved vessels (12.9%) were highly associated with cure and beneficial treatment effects. Pale halos surrounding brown dots (8.0%) and arborizing vessels (9.8%) were mainly correlated with skin lesion alleviation. Mixed vessels (12.9%), a grey-whitish veil (11.7%) and reticular patterns (11.0%) were mainly associated with no effect. The differences between each subgroup were statistically significant (P = 0.000)., Conclusions: There is a clear correlation between the efficacy of PDT and the dermoscopy pattern in patients with PWS. Dermoscopy may therefore provide very useful clinical information prior to treatment in these cases. In addition, the vascular manifestations of PWS determined by dermoscopy help to predict response to PDT and manage patient expectations., (© 2020 European Academy of Dermatology and Venereology.)

Purpose: To evaluate the long-term follow-up of patients with a circumscribed choroidal hemangioma (CCH) treated with limited single spot photodynamic therapy (PDT) at the Amsterdam University Medical Center, location AMC (AUMC)., Methods: This cross-sectional study included 17 patients, treated between 2001 and 2012. Evaluation included best corrected visual acuity, slitlamp examination, fundoscopy, ophthalmic ultrasonography (USG), fluorescein/indocyanine green angiography (FA/ICG), fundus autofluorescence (FAF) and optical coherence tomography (OCT)., Primary Outcome: recurrence rate, secondary outcomes: long-term functional and structural changes., Results: An unexpected high recurrence rate of 35% (n6) was found with a mean follow-up time between treatment and recurrence of almost 6 years, range 2.8-10.7 years. With a recurrence, the classical CCH pattern was no longer recognizable on FA or ICG. Signs of leakage were best observed with OCT, and the recurrence could be confirmed with USG. Retreatment with PDT of all recurrences was successful. After a successful initial PDT, the achieved visual acuity (VA) showed a small decrease over time, median VA from 0.10 LogMar to 0.15 LogMar (p 0.09) after a mean follow-up of 11.36 years (range 5.1-15.5 years). During follow-up study visit, the OCT revealed a slightly increased thickness of the choroid in 86% of cases at the site of the original tumour, without a clear correlation to the recurrences., Conclusion: Limited single spot PDT is a safe and effective treatment for CCH preserving a good VA. However, because of the relatively high recurrence rate found in this study, we recommend regular follow-up with OCT every 6 months., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: We know the efficacy of daylight phototherapy dynamic (DL-PDT) in the treatment of actinic keratosis (AK). But the almost studies have compared daylight with red light using methyl aminolevulinate cream and not with blue light. PDT with blue light is another conventional PDT that is effective in the treatment of AKs., Objectives: The aim of this study is to assess the efficacy and the safety of DL-PDT vs. PDT in blue light in the treatment of AKs., Methods: This randomized, controlled, intra-individual efficacy and safety study enrolled 26 subjects. AKs on the face/scalp were treated once, with DL-PDT on one side and c-PDT on the contralateral side. Primary endpoints for DL-PDT at week 12 were efficacy with clearance of AKs and safety with assessment of pain. Lesions with complete response 12 weeks after one treatment session were followed until week 24., Results: More than 1000 AK were studied. At week 12, the raw number of disappeared AK lesions at 3-month follow-up was 19.6 (±6.0) for DL-PDT and 20.0 (±6.9) for c-PDT with P = 0.8460 (90.5% vs. 94.2% of AK disappearance, respectively). The response was maintained at 6 months (90.0% and 94.6% of AK reduction, respectively). DL-PDT was nearly painless than c-PDT with light blue: 1.2 vs. 5.1, respectively (P < 0.0001)., Conclusions: Daylight-PDT seems as effective as c-PDT with light blue and DL-PDT is less painful. The response of DL-PDT was sustainable until 6 months., (© 2020 European Academy of Dermatology and Venereology.)

Objectives: The study examines the changes in dermoscopic features of actinic keratosis (AK) after photodynamic therapy, and delineates the association between AK dermoscopic and histopathological findings., Methods: A total of 21 patients (23 lesions) with pathologically confirmed actinic keratosis who received 5-aminolaevulinic acid (ALA) photodynamic therapy (ALA-PDT) were enrolled. The numbers of PDT treatments were: 1, n = 1; 2, n = 2; 3, n = 10; 4, n = 6; 5, n = 2; 6, n = 2). The dermoscopic features before and after the PDT were compared., Results: There were statistically significant decreases in the positive rates of dermoscopic features including scales (P < 0.001), follicular plugs with whitish halo (P = 0.013), and red pseudonetwork (P = 0.022) among patients treated with ALA-PDT. Dermoscopic feature was significantly associated with pathological grade (P < 0.001). Histopathological hyperkeratosis was significantly associated with dermoscopic red pseudonetwork (P = 0.034) and wavy vessel (P = 0.005). Parakeratosis was associated with wavy vessels (P = 0.001). For vascular hyperplasia in dermal papillae, the significant correlates included scales (P = 0.011), follicular plugs with whitish halo (P = 0.011), red pseudonetwork (P < 0.001); coiled vessels (P = 0.003) and rosette sign (P = 0.004). Wavy vessels was the only feature correlating keratosis pilaris (P = 0.003)., Conclusions: The findings of the present study support dermoscopy as having potential to be useful for diagnosing and monitoring of actinic keratosis., (© 2020 The Australasian College of Dermatologists.)

Background: Organ transplant recipients (OTR) have a higher risk of actinic keratosis (AK) and keratinocyte carcinomas (KC). There are no clinical trials assessing the effectiveness of daylight photodynamic therapy (DPDT) to prevent new AK and KC in OTR., Objectives: To determine whether repeated treatments of field cancerization with DPDT are effective in preventing new AK and KC in OTR., Methods: A randomized, intra-subject controlled, evaluator-blind, split-face and/or scalp trial, from April 2016 to October 2018. Participants were OTR older than 18 years, 1-year posttransplant, with at least 5 AK on each hemi-face/hemi-scalp. One side received six field treatments with DPDT: two sessions 15 days apart at baseline, two at 3 months and two at 9 months after baseline. Control side received lesion-directed treatment with cryotherapy (double freeze-thaw) at baseline, 3 and 9 months. Total number of lesions (AK and KC) at 21 months, number of new AK and KC at 3, 9, 15 and 21 months and treatment preferences were analysed., Results: Of 24 men included, 23 were analysed at 3 months; and 21, at 9, 15 and 21 months. Mean (SD) age was 69.8 years (9.2). The total number of lesions at 21 months was 4.7 (4.3) for DPDT and 5.8 (5.0) for control side; P = 0.09. DPDT showed significantly lower means [SD] of new lesions compared to control side at 3 months (4.2 [3.4] vs. 6.8 [4.8]; P < 0.001), 9 months (3.0 [3.3] vs. 4.3 [3.4]; P = 0.04) and 15 months (3.0 [4.6] vs. 4.8 [5.0]; P = 0.02), and non-significant at 21 months (3.7 [3.5] vs. 5.0 [4.5]; P = 0.06). Most participants preferred DPDT., Conclusion: DPDT showed potential effectiveness in preventing new AK and KC in OTR by consecutive treatments of field cancerization. The preference for DPDT could facilitate adherence to the long-term treatment necessary in these patients., (© 2019 European Academy of Dermatology and Venereology.)

Background: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons., Objectives: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes., Methods: Patients with ≥5 Olsen II AKs in a 25 cm 2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area., Results: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS., Conclusions: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots., (© 2019 European Academy of Dermatology and Venereology.)

Purpose: To compare the efficacy, safety and stability of standard epithelium-off cross-linking (SCXL) versus accelerated epithelium-off cross-linking (ACXL) and transepithelial epithelium-on cross-linking (TCXL) in the treatment of progressive keratoconus (KC) in children., Methods: This prospective multicentre controlled trial included 271 eyes (136 children) with grade 1-3 progressive KC who were randomized to undergo SCXL (n = 91, as a control group), ACXL (n = 92) or TCXL (n = 88). Uncorrected and corrected distance visual acuity, subjective refraction, pachymetry, keratometry and corneal topography measurements were recorded preoperatively and 6, 12 and 24 months postoperatively., Results: At 1 year, there was no significant difference in uncorrected distance visual acuity, refractive sphere, cylinder, spherical equivalent or Kmax between the ACXL and SCXL groups; however, during year 2, ACXL regressed while SCXL continued to improve. After 2 years, there were significant differences in all visual, refractive and keratometric components between SCXL and both ACXL and TCXL (p < 0.0001) and between ACXL and TCXL (p < 0.0001). KC progressed in 5.4% of patients who had ACXL and 28.4% of those who had TCXL but in none of those who had SCXL. Vernal keratoconjunctivitis was documented in 43.3% of eyes that progressed postoperatively., Conclusion: SCXL was more effective for paediatric KC and achieved greater stability than either ACXL or TCXL, and ACXL was superior to TCXL. SCXL also achieved marked improvement in both myopia and spherical equivalent; however, these refractive outcomes were unpredictable and uncontrollable. TCXL had a 28.4% failure rate within 2 years. SCXL is preferable for management of paediatric KC., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate photorefractive intrastromal cross-linking (PiXL) treatment for low-grade myopia, comparing three treatment protocols., Methods: Healthy individuals, 25.6 ± 3.6 years of age, with low-grade myopia underwent epi-on PiXL with either: 4-mm zone treated in high oxygen environment (4 mm-HIGH; n = 15), 4-mm/room air (4-mm LOW; n = 6), or 6-mm/high oxygen (6-mm HIGH; n = 6). Efficacy was determined by change in uncorrected visual acuity (UCVA), manifest refractive spherical equivalent (MRSE) and corneal curvature (K mean ) over a 12-month follow-up. Safety was determined by best spectacle corrected visual acuity (BSCVA), corneal endothelial cell loss and registration of side-effects., Results: Twenty-seven subjects were included. Due to insufficient effect with the 4-mm LOW treatment and an unacceptable degree of initial light sensitivity/ocular irritation in the 6-mm HIGH group, the inclusions to these treatments were stopped after inclusion of 6 patients in each group. The 4-mm HIGH treatment showed a significantly larger improvement in UCVA (-0.45 ± 0.27 LogMAR) and MRSE (+0.99 ± 0.44 D) at 1, 6 and 12 months compared with the 4-mm LOW treatment (p < 0.05). At 12 months posttreatment, endothelial cell count and BSCVA were unaltered. More initial side-effects were noted with the 6-mm HIGH treatment, compared with the 4-mm HIGH treatment (p < 0.05)., Conclusion: Epi-on PiXL may become a safe and effective non-ablative treatment for low-grade myopia. The effect is augmented by high oxygen environment and remains stable for 12 months. The initial ocular irritation is acceptable with a 4-mm treatment zone. The present results justify further clinical studies on PiXL, including refinements of the technique and long-term results., (© 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background/objectives: Side effects of current treatments and the need for a safe treatment with higher efficiency necessitate seeking new treatment options for vitiligo. Few studies have investigated the combination of psoralen with narrowband ultraviolet B (NBUVB). In this study, we compared the efficacy and safety of psoralen and NBUVB combination (P-NBUVB) with NBUVB alone in treatment of vitiligo., Methods: This randomised clinical trial was carried out during 2015-2017 in dermatology clinics of Ghaem and Imam Reza hospitals, Mashhad, Iran on 40 vitiligo patients with 5-60% body involvement. The patients were randomly divided into two groups of NBUVB alone and P-NBUVB. Both groups underwent 60 phototherapy sessions (three sessions per week), and the repigmentation rate was measured using vitiligo area severity index (VASI) score. SPSS v. 16 software and appropriate statistical tests were used to analyse the data. P < 0.05 was considered statistically significant., Results: The mean age of patients was 33.9 ± 11.3 years. Twenty patients (50%) were females. The P-NBUVB group showed greater VASI improvement in lower extremities (P = 0.003) and overall (P = 0.026) compared with NBUVB group. Moreover, the treatment response appeared sooner in P-NUVB group., Conclusion: Based on our results, we can conclude that adding psoralen to NBUVB phototherapy can result in increased efficacy. However, more studies are needed to evaluate the long-term effects and side effects of this treatment., (© 2019 The Australasian College of Dermatologists.)

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3-h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well-tolerated therapy although discomfort associated with conventional protocol may require pain-reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence., (© 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Guidelines for photodynamic therapy (PDT) of actinic keratosis (AK) recommend pretreatment with curettage. The impact of curettage on cure rate is, however, not well established., Objective: The present study aimed to evaluate whether daylight PDT without curettage could be as effective as daylight PDT with curettage., Methods: Twenty-five patients with multiple AKs were treated in two even-sized areas on the face and scalp. One area was treated with standard daylight PDT starting with curettage followed by incubation with methyl aminolevulinate (MAL) for 30 min before 2 h of daylight exposure. The other area was incubated with MAL for 1 h without prior curettage before 2 h of daylight exposure. The longer incubation time was used to obtain a sufficiently high protoporphyrin IX concentration in the non-curettaged area., Results: There was no difference in cure rate 3 months after daylight PDT in areas pretreated with curettage (86%) compared to non-curettaged areas (84%) (P = 0.1). Neither was there any difference between reported pain during daylight exposure (P > 0.7) or clinically evaluated erythema the day after treatment (P = 1.0)., Conclusion: Daylight PDT without curettage but with 1 h of MAL incubation before daylight exposure was shown to be as effective in treatment of thin AKs on the face and scalp as standard daylight PDT with curettage. This modification of daylight PDT eases the task for the clinic and makes it more convenient for the patients as well, creating the possibility of performing daylight PDT as an entirely home-based treatment for AKs of the face and scalp without training the patients to perform pretreatment., (© 2019 European Academy of Dermatology and Venereology.)

Leishmaniasis is a vector borne disease transmitted by phlebotomine sandflies. Cutaneous leishmaniasis (CL) predominantly causes skin ulcers but may disseminate. CL may present a therapeutic challenge. The present study reports the case of a 15-year old boy with CL consisting of a single, ulcer on the leg, resistant to pentavalent antimony, oral fluconazole and topical ketoconazole therapy. Repeated photodynamic therapy using aminolevulinic acid resulted in complete healing of the ulcer, suggesting utility of this approach in resistant cases of CL., (© 2019 Wiley Periodicals, Inc.)

Purpose: To compare the safety and efficacy of standard 30 min epithelium-off cross-linking (CXL) versus photorefractive keratectomy (PRK) combined with accelerated epithelium-off cross-linking (AXL) for the treatment of progressive keratoconus (CXL-Plus)., Methods: This study was a prospective multicentre comparative clinical study. A total of 125 eyes of 75 patients with grade 1 keratoconus and documented progression were divided into two groups. Group A included 58 eyes treated with standard CXL. Group B included 67 eyes treated with combined PRK and AXL. The recorded data included UDVA, CDVA, subjective and objective refraction, keratometry and pachymetry using corneal topographies preoperatively and postoperatively at 3, 6, 12 and 24 months of follow-up., Results: In group A, at 24 months of UDVA and CDVA were improved from 1.12 ± 0.38 and 0.58 ± 0.42 to 0.66 ± 0.20 and 0.20 ± 0.12 (LogMAR±SD). The spherical equivalent was reduced from 4.03 ± 1.18 to 1.78 ± 1.04 D. The cylinder reduction was 0.32 ± 0.19 D. In group B, at 24 months of UDVA and CDVA were improved from 1.26 ± 0.52 and 0.68 ± 0.36 to 0.58 ± 0.28 and 0.20 ± 0.16 (LogMAR ± SD). The spherical equivalent was reduced from 4.23 ± 0.95 to 1.92 ± 0.74 D. The cylinder reduction was ±1.76 D., Conclusion: Surprisingly, standard CXL showed close results to CXL-Plus at the 24th follow-up month. Standard CXL acted as a stabilizing procedure associated with a late myopic component reduction. CXL-Plus acted as a refractive and stabilizing procedure with an early effect on both the myopic and the astigmatic component but no later improvements. Standard CXL seems to be more powerful than AXL in its long-term effect. Therefore, in the future, we want to test the combination of PRK with standard CXL., (© 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the effect of corneal collagen cross-linking (CXL) on progressive keratoconus using 0.1% riboflavin with either dextran or methylcellulose as the main supplement., Methods: In a comparative case series, CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing either dextran (dextran-riboflavin; n = 20) or methylcellulose (methylcellulose-riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug tomography, maximal keratometry reading (K max ), visual acuity (VA) and endothelial cell density (ECD) were recorded. Stromal changes one month after surgery were analysed using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM)., Results: The CCT was significantly higher in the methylcellulose-riboflavin group during the CXL procedure. The IVCM demarcation line depth was 274 ± 80 (SD) μm in the dextran-riboflavin group and 442 ± 80 μm in the methylcellulose-riboflavin group (p < 0.001). Complete absence of keratocytes in the pre-endothelial stroma was found in none of the corneas treated with dextran-riboflavin and in 42% of the corneas treated with methylcellulose-riboflavin. Visibility of the OCT demarcation line was significantly lower in the methylcellulose-riboflavin group. K max and corrected distance visual acuity were improved in the methylcellulose-riboflavin group and stable in the dextran-riboflavin group after 2 years. Endothelial cell density (ECD) was stable in both groups., Conclusion: We found deeper structural changes in the methylcellulose-riboflavin group than in the dextran-riboflavin group. This may be explained by different riboflavin solution properties and raises safety concerns. The study also indicates improved effect using methylcellulose-riboflavin than dextran-riboflavin, possibly explained by deeper stromal CXL effect., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies., Objective: To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT., Patients and Methods: An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded., Results: Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation)., Conclusions: Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability., (© 2019 European Academy of Dermatology and Venereology.)

Purpose: To compare results between standard and accelerated corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus., Methods: We performed literature searches in PubMed, Cochrane Library, Web of Science, ISRCTN registry, ClinicalTrials.gov, and EMBASE for studies comparing conventional Dresden (C-CXL) and accelerated CXL (A-CXL). Outcomes were clinical results and changes in corneal properties. Weighted mean differences were used to evaluate the effects., Results: Here, 22 studies with 1158 eyes (C-CXL: 577 eyes; A-CXL: 581 eyes) were included. At the last follow-up, C-CXL was superior regarding minimum keratometry (p < 0.00001) and demarcation line depth (p < 0.00001), whereas A-CXL should be favoured when considering minimum corneal thickness (p = 0.0005). No differences in uncorrected and corrected distance visual acuity (p = 0.09 and 0.98), spherical equivalent (p = 0.11), spherical and cylindrical error (p = 0.29 and 0.32), maximal and average keratometry (p = 0.05 and 0.65), central corneal thickness (p = 0.15), corneal biomechanical properties (p ≥ 0.21 respectively), time of reepithelialization (p = 0.76), subbasal nerve density (p = 0.69), endothelial cell density (p = 0.30) and morphology (p ≥ 0.40 respectively) were found among both groups., Conclusion: Consideration of less corneal thinning favours A-CXL, whereas the deeper demarcation line and greater changes in minimum keratometric values in C-CXL may indicate a higher treatment efficacy. Altogether, C-CXL, as well as A-CXL, provides successful results in the strengthening of corneal tissue., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To compare the antifungal efficacy of corneal collagen cross-linking with photoactivated riboflavin (PACK-CXL) and voriconazole in experimental Fusarium solani and Candida albicans keratitis models., Methods: Sixty-four corneas of 32 New Zealand rabbits were included and divided into two main groups. Intrastromal injection of Fusarium and Candida suspensions was performed, and it was observed that keratitis was formed on the third day. Both groups were randomly separated into the following four groups: control, PACK-CXL, voriconazole and PACK-CXL combined with voriconazole. PACK-CXL was applied using 0.25% riboflavin in an accelerated Dresden protocol (total ultraviolet A dose 5.4 J/cm²). Voriconazole was applied topically as 7x1/day with a dose of 1% (10 mg/ml). Corneal buttons were excised on the tenth day, and microbiological and pathological examinations were performed., Results: The PACK-CXL and PACK-CXL combined with voriconazole groups each had 100 colony-forming unit (CFU/ml) of reproduced micro-organisms compared with 500 CFU/ml in the voriconazole group and 1500 CFU/ml in the control group (p < 0.001) in the Fusarium keratitis model. The PACK-CXL combined with voriconazole group had 100 CFU/ml, the PACK-CXL group had 150 CFU/ml, and the voriconazole group had 200 CFU/ml of reproduced micro-organisms compared with 4000 CFU/ml in the control group (p < 0.002) in the Candida keratitis model. (p < 0.001). Fewer hyphae and non-specific stromal changes were observed in the pathological cross sections examined in subgroups that used CXL., Conclusion: There was less fungus reproduction and a lower keratitis score for Fusarium solani and Candida albicans in the treatment groups compared to the control groups, especially in groups that used PACK-CXL. These results suggest that it is useful to combine PACK-CXL treatment with medical treatment in the fungal keratitis algorithm at the early stage of the disease., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To describe clinical characteristics and response to verteporfin therapy (PDT) in eyes with retinal pigment epithelium detachment (PED) in the absence of primary disease other than characteristics compatible with central serous chorioretinopathy (CSC)., Methods: Retrospective review of 634 consecutive patients diagnosed with isolated PED or CSC in one or both eyes in the period from 2007 to 2014 at a single institution., Results: Pigment epithelium detachment (PED) in the absence of primary pathology other than angiographic choroidal hyperpermeability in the incident or fellow eye or manifest CSC in the fellow eye was found in 22 eyes in 19 patients. Follow-up ranged from 4 to 61 months. Five of 19 patients (26%) had classic CSC in the fellow eye. Transition from isolated PED to manifest CSC in the eye with PED was observed in seven eyes (33%) over a median untreated period of observation of 11 months (range, 1-32 months). A single session of PDT followed up 1-6 months later showed full resolution of the PED in seven (78%) of nine eyes. Of the 13 untreated eyes, five eyes (38%) underwent spontaneous resolution of the PED., Conclusion: Fellow-eye findings, conversion to CSC, resolution of PED after PDT or, less commonly, spontaneously support that isolated PED is a manifestation of CSC that represents an intermediate stage between pachychoroid and classic CSC. The chance of experiencing resolution of the PED was roughly twice as high with PDT as with untreated observation., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)