Three-Year Results of Simultaneous Transepithelial Phototherapeutic Keratectomy and Conventional Photorefractive Keratectomy (Cretan Protocol Plus) Followed by Corneal Crosslinking for Keratoconus.

PURPOSE: The aim of this study was to present the 3-year outcomes after simultaneous transepithelial phototherapeutic keratectomy (t-PTK) and conventional photorefractive keratectomy (PRK) followed by corneal crosslinking (CXL) for keratoconus. METHODS: In this prospective, interventional case series, patients with progressive keratoconus underwent simultaneous t-PTK and conventional PRK followed by CXL (Cretan protocol plus). Visual, refractive, and topographic outcomes were evaluated along with endothelial cell density (ECD) preoperatively and at 1, 2, and 3 years postoperatively. RESULTS: Twenty-two patients (31 eyes) were enrolled. No intraoperative or postoperative complications were observed in any of the patients. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected and mean corrected distance visual acuity improved from 0.81 ± 0.40 and 0.18 ± 0.21 preoperatively to 0.38 ± 0.33 ( P < 0.001) and 0.06 ± 0.12 ( P < 0.001) at 3-year follow-up. Mean spherical equivalent improved from -5.39 ± 3.89 diopters (D) preoperatively to -2.29 ± 2.65 D ( P < 0.001) at 3 years postoperatively. Mean corneal astigmatism reduced from -4.70 ± 2.86 D preoperatively to -3.55 ± 2.45 D ( P = 0.001) at 3 years postoperatively. No ECD alterations were observed throughout the 3-year follow-up ( P > 0.05). CONCLUSIONS: Simultaneous t-PTK and conventional PRK followed by CXL seems to be an effective and safe treatment for progressive keratoconus over 3-year follow-up.

Individualized dosimetry in Ru-106 ophthalmic brachytherapy based on MRI-derived ocular anatomical parameters.

PURPOSE: To estimate ocular geometry-related inaccuracies of the dosimetric plan in Ru-106 ophthalmic brachytherapy. METHODS AND MATERIALS: Thirty patients with intraocular lesions were treated with brachytherapy using a Ru-106 plaque-shell of inner radius of 12 mm. Magnetic resonance imaging was employed to determine the external scleral radius at tumor site and the tumor margins. A mathematical model was developed to determine the distance between the external sclera and the internal surface of the plaque associated with the tangential application of the plaque on the treated eye. Differences in delivered dose to the tumor apex, sclera and tumor margins as derived by considering the default eye-globe of standard size (external sclera radius = 12 mm) against the individual-specific eye globe were determined. RESULTS: The radius of external sclera at the tumor site was found to range between 10.90 and 13.05 mm for the patient cohort studied. When the patient specific eye-globe/tumor geometry is not taken into account, the delivered dose was found to be overestimated by 8.1% ± 4.1% (max = 15.3%) at tumor apex, by 1.5% ± 2.8% (max = 5.7%) at anterior tumor margin, by 16.6% ± 7.5% (max = 36.4%) at posterior tumor margin and 8.1% ± 3.8% (max = 13.2%) at central sclera of eyes with lower than the default radius. The corresponding dose overestimations for eyes with higher than the default radius was 13.5% ± 4.3% (max = 22.3%), 1.5% ± 2.8% (max = 5.7%), 12.6% ± 4.5% (max = 20.0%), and 15.1% ± 5.0% (max = 24.4%). CONCLUSIONS: The proposed patient-specific approach for Ru-106 brachytherapy treatment planning may improve dosimetric accuracy. Individualized treatment planning dosimetry may prevent undertreatment of intraocular tumors especially for highly myopic or hyperopic eyes.

Late-onset inverse Bell's phenomenon after upper eyelid trauma.

Bell's phenomenon evaluation is an important part of preoperative patient assessment for eyelid surgeries. Inverse Bell's phenomenon is a rare manifestation, usually observed in the early postoperative period following ptosis restoration surgeries, in pathological conditions, and in a small proportion of normal population. In the current case report, a 6-year-old girl presented with late-onset posttraumatic inverse Bell's phenomenon, 6 months after facial trauma with posttraumatic lagophthalmos. Rehabilitative blepharoplasty for the correction of lagophthalmos led to the restoration of inverse Bell's phenomenon 3 months postoperatively. Potential causative mechanisms are discussed for this late-onset manifestation of inverse Bell's response.

Association between HPV detection in swab samples and tissue specimens and ophthalmic pterygium recurrence.

PURPOSE: To investigate the presence of HPV on the ocular surface after surgical excision of HPV infected pterygia and the possible correlation of HPV with pterygium postoperative recurrence. MATERIALS AND METHODS: Both exfoliative pterygium swab samples and respective tissue specimens were received and analyzed with real-time PCR for the detection of HPV-infected pterygia. In addition, swab samples from patients that had HPV-infected pterygia with no recurrence after 1 year of follow-up, as well as swab samples from patients with healthy conjunctiva, were analyzed. RESULTS: Forty eyes with pterygium of 40 patients and 40 eyes with normal conjunctiva were included in the study. HPV virus was detected in the tissue specimens of 11 patients (27.5%) and in the swabs of 9 patients (22.5%). The HPV subtypes detected were 33, 39, 45, 56, 59, 66, and 68. The swab test had sensitivity of 81.82% and 100% specificity. In 15 (43%) patients, a bare sclera technique was used for pterygium removal and eleven of these patients showed recurrence of the disease. Surgical excision with use of autologous conjunctival graft was performed in twenty patients and five of them had recurrence. Patients with recurrent disease were 12.41 times more likely to have an HPV-infected pterygium (p = 0.031). Furthermore, from the 11 HPV positive patients, six had no recurrence, 1 year after surgery. In five of them, a swab sample was taken from the site of the surgical excision 1 year after surgery and real-time PCR was negative for HPV presence. CONCLUSION: Persistence of HPV infection seems to be correlated with postoperative pterygium recurrence. Further investigation with the use of the minimally invasive proposed swab technique may contribute in the understanding of pterygium pathogenesis and in the development of a more efficient treatment planning.

Dual-energy CT imaging of orbits during episcleral brachytherapy with Ru-106 plaques: A phantom study on its potential for plaque position verification.

PURPOSE: To investigate the potential of dual energy CT (DECT) to suppress metal artifacts and accurately depict episcleral brachytherapy Ru-106 plaques after surgical placement. METHODS: An anthropomorphic phantom simulating the adult head after surgical placement of a Ru-106 plaque was employed. Nine DECT acquisition protocols for orbital imaging were applied. Monochromatic 140 keV images were generated using iterative reconstruction and an available metal artifact reduction algorithm. Generated image datasets were graded by four observers regarding the ability to accurate demarcate the Ru-106 plaque. Objective image quality and visual grading analysis (VGA) was performed to compare different acquisition protocols. The DECT imaging protocol which allowed accurate plaque demarcation at minimum exposure was identified. The eye-lens dose from orbital DECT, with and without the use of radioprotective bismuth eye-shields, was determined using Monte Carlo methods. RESULTS: All DECT acquisition protocols were judged to allow clear demarcation of the plaque borders despite some moderate streaking/shading artifacts. The differences between mean observers' VGA scores for the 9 DECT imaging protocols were not statistically significant (p > 0.05). The eye-lens dose from the proposed low-exposure DECT protocol was found to be 20.1 and 22.8 mGy for the treated and the healthy eye, respectively. Bismuth shielding was found to accomplish >40% reduction in eye-lens dose without inducing shielding-related artifacts that obscure plaque delineation. CONCLUSIONS: DECT imaging of orbits after Ru-106 plaque positioning for ocular brachytherapy was found to allow artifact-free delineation of plaque margins at relatively low patient exposure, providing the potential for post-surgery plaque position verification.

Long-term Comparison of Combined t-PTK and CXL (Cretan Protocol) Versus CXL With Mechanical Epithelial Debridement for Keratoconus.

PURPOSE: To compare the long-term outcomes of corneal cross-linking (CXL) for the treatment of keratoconus using two different techniques for epithelial removal: transepithelial phototherapeutic keratectomy (t-PTK) and mechanical epithelial debridement. METHODS: In this prospective, comparative, interventional case series, 26 patients (30 eyes) with progressive keratoconus underwent CXL treatment. Fifteen eyes (13 patients) underwent epithelial removal with t-PTK (Cretan protocol) and 15 eyes (13 patients) underwent mechanical epithelial debridement (Dresden protocol) during CXL. Visual, refractive, and keratometric outcomes were evaluated preoperatively and at 1, 2, 3, and 4 years postoperatively. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. In the Cretan protocol group, mean uncorrected (UDVA) and corrected (CDVA) visual acuity improved from 0.99 ± 0.42 and 0.33 ± 0.28 logMAR preoperatively to 0.75 ± 0.32 (P = .018) and 0.21 ± 0.16 (P = .024) logMAR at 4 years postoperatively, respectively. In the Dresden protocol group, mean UDVA improved from 0.83 ± 0.47 logMAR preoperatively to 0.63 ± 0.40 logMAR (P = .033) at 4 years postoperatively, whereas mean CDVA did not demonstrate a statistically significant improvement postoperatively (P > .05). In the Cretan protocol group, mean corneal astigmatism improved from -6.19 ± 4.54 diopters (D) preoperatively to -4.68 ± 3.10 D (P = .041) at last follow-up, whereas in the Dresden protocol group there was no statistically significant difference postoperatively (P > .05). CONCLUSIONS: Epithelial removal with t-PTK during CXL (Cretan protocol) resulted in better visual, refractive, and keratometric outcomes compared with mechanical epithelial debridement over a long-term follow-up. [J Refract Surg. 2019;35(10):650-655.].

Mini descemet membrane stripping (m-DMES) in patients with Fuchs' endothelial dystrophy: A new method.

We present two cases with focal corneal edema due to Fuchs' endothelial dystrophy that were successfully treated with mini Descemet membrane stripping (m-DMES) (diameter of 3-4 mm; at the area of preexisting focal corneal edema) without endothelial replacement during cataract surgery. Specular microscopy demonstrated Fuchs' endothelial dystrophy and histopathologic evaluation confirmed the diagnosis. Anterior segment optical coherence tomography and confocal microscopy were used for the evaluation of the corneal tissue recovery course after the surgical procedure. In both patients, we observed an initial aggravation of corneal edema in the area of DM removal for two months followed by gradual improvement. At four months postoperatively, corneal edema had completely regressed resulting in corneal clearance and visual acuity improvement in both cases. M-DMES without graft insertion represents a promising alternative surgical technique that could be applied in specific cases of Fuchs' endothelial dystrophy with focal corneal edema.

Corneal Stromal Demarcation Line Depth Following Standard and a Modified High Intensity Corneal Cross-linking Protocol.

PURPOSE: To compare the corneal stromal demarcation line depth using anterior segment optical coherence tomography (AS-OCT) after corneal cross-linking (CXL) using two different treatment protocols: the standard Dresden protocol (30 minutes with 3 mW/cm(2)) and a modified high intensity protocol (7 minutes with 18 mW/cm(2)), corresponding to a total surface dose of 5.4 and 7.5 J/cm(2), respectively. METHODS: This prospective, comparative, interventional case series included 29 keratoconic patients (32 eyes). All patients underwent CXL using the same high intensity ultraviolet-A (UV-A) irradiation device (CCL-365; Peschke Meditrade GmbH, Huenenberg, Switzerland). Sixteen eyes were treated for 30 minutes with 3 mW/cm(2) according to the standard Dresden protocol, whereas 16 eyes were treated with a novel modified high intensity CXL protocol for 7 minutes with 18 mW/cm(2) of UV-A irradiation intensity. One month postoperatively, corneal stromal demarcation line depth was measured by two independent observers using AS-OCT. RESULTS: There was no significant difference in corneal stromal demarcation line depth between observer measurements for both groups (P = .645, Dresden protocol group; P = .715, high intensity group). Mean corneal stromal demarcation line depth was 341.81 ± 47.02 µm for the Dresden protocol group and 313.37 ± 48.85 µm for the high intensity protocol group. There was no statistically significant difference (P = .104) in the corneal stromal demarcation line depth between the two groups. Mean endothelial cell density did not change significantly in either group (P = .090, Dresden protocol group; P = .103, high intensity group). No intraoperative or postoperative complications were noted. CONCLUSIONS: Corneal stromal demarcation line depth using UV-A irradiance with 3 mW/cm(2) for 30 minutes and 18 mW/cm(2) for 7 minutes was similar. It seems that the current modified accelerated CXL protocol provided the same treatment depth as the standard Dresden protocol.

Multiorganism, drug-resistant keratitis treated by corneal crosslinking.

PURPOSE: To describe a case of multiorganism, drug-resistant keratitis that responded well to corneal crosslinking (CXL) treatment. METHODS: A 52-year-old man presented to our institute with a 2-month ocular history of infectious keratitis in his right eye, on topical antibacterial, antifungal, and antiprotozoan treatment, and complained of increase in pain, discomfort, and visual deterioration. Slit-lamp examination revealed advanced infectious keratitis (extensive deep corneal infiltrate with perineuritis). Cultural and molecular analysis of obtained corneal specimens demonstrated combined fungal and Acanthamoeba infection; confocal microscopy confirmed Acanthamoeba infection. Intense targeted topical antifungal and antiprotozoan treatment was initiated immediately and 1 month later CXL was performed due to drug resistance of the infection. RESULTS: Two weeks after CXL treatment, the corneal findings had deteriorated, while a corneal abscess was formed and extended at almost half of the cornea. This was gradually limited and the corneal infiltrate and abscess were eventually decreased. In addition, the symptoms improved. CONCLUSIONS: Corneal crosslinking could be an effective therapy in the management of advanced infectious keratitis unresponsive to conventional medical treatment.

Pupil response to tropicamide following corneal crosslinking.

PURPOSE: To evaluate the effect of corneal crosslinking (CXL) with ultraviolet A (UVA) irradiation on pupil response to tropicamide 0.5% instillation. METHODS: This prospective interventional study enrolled 17 patients (19 eyes) with progressive keratoconus who underwent CXL with UVA irradiation. Central corneal thickness (CCT) was evaluated with the use of anterior segment optical coherence tomography (Visante OCT 3.0). Pupil diameter was measured with the use of Colvard infrared pupillometer before the instillation of tropicamide 0.5% and after the instillation of tropicamide every 5 minutes for total duration of 30 minutes. Corneal epithelial integrity was examined with the use of fluorescein dye staining. Measurements were performed 1 day preoperatively and 1 month postoperatively, with emphasis on simulating the same light conditions regarding the pupil measurements. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. Mean CCT decreased significantly (p<0.001) 1 month postoperatively. Mean postoperative pupil size did not change significantly at any time point compared to the mean preoperative measurements. CONCLUSIONS: The CXL procedure seems not to impair effectiveness of topical drugs, using pupil size measurements after tropicamide 0.5% instillation.

Effect of the Regenerative Agent Poly(Carboxymethylglucose Sulfate) on Corneal Wound Healing After Corneal Cross-Linking for Keratoconus.

PURPOSE: To evaluate the effect of a regenerative agent (RGTA) [Cacicol20-poly(carboxymethyl glucose sulfate); OTR3, Paris, France] on corneal reepithelialization and pain after corneal cross-linking (CXL) for keratoconus. METHODS: In this prospective comparative (contralateral) clinical study, patients with bilateral progressive keratoconus underwent CXL treatment. The corneal epithelium during CXL was removed using transepithelial phototherapeutic keratectomy (Cretan protocol). One eye of each patient was randomly instilled with an RGTA (Cacicol20) once a day (study group), whereas the fellow eye was instilled with artificial tears (control group). Patients were examined daily until complete reepithelialization. Postoperative examinations included slit-lamp biomicroscopy to assess the epithelial defect size and subjective evaluation of pain. RESULTS: The study enrolled 18 patients (36 eyes). The mean epithelial defect size for study and control groups was 19.6 ± 4.2 mm versus 21.5 ± 2.8 mm, respectively, at day 1 (P = 0.019) and 6.4 ± 3.4 mm versus 7.9 ± 4.3 mm, respectively, at day 2 (P = 0.014). At day 3 postoperatively, 61.1% of study eyes were fully reepithelialized, compared with 11.1% of control eyes (P = 0.002). CONCLUSIONS: RGTA (Cacicol20) instillation seems to result in faster corneal reepithelialization after CXL in this study. However, there was no significant effect in subjective pain/discomfort.

Corneal stromal demarcation line determined with anterior segment optical coherence tomography following a very high intensity corneal collagen cross-linking protocol.

PURPOSE: To evaluate corneal stromal demarcation line depth after very high intensity (18 mW/cm) ultraviolet-A irradiation for a 5-minute corneal collagen cross-linking (CXL) protocol with the use of anterior segment optical coherence tomography. METHODS: This prospective interventional study enrolled 14 patients (18 eyes) with progressive keratoconus who underwent CXL with an ultraviolet-A irradiation intensity of 18 mW/cm for 5 minutes. One month postoperatively, corneal stromal demarcation line depth was measured with the use of anterior segment optical coherence tomography by 2 independent observers. The rate of reepithelialization and endothelial cell density at a 3-month follow-up period were also evaluated. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. No statistically significant difference between the 2 observers' measurements was observed (P = 0.989). Mean corneal stromal demarcation line depth was 223 ± 32 µm (range, 159-265 µm). The mean endothelial cell density decreased from 2714 ± 174 preoperatively to 2671 ± 192 at 3 months postoperatively; however, this decrease was not statistically significant (P = 0.221). CONCLUSIONS: Corneal stromal demarcation line depth after a very high intensity 5-minute CXL protocol seems to be shallower than the standard Dresden protocol.

Excessive Corneal Flattening and Thinning After Corneal Cross-linking: Single-Case Report With 5-Year Follow-up.

PURPOSE: To present a case of significant progressive corneal flattening and thinning after corneal cross-linking (CXL), with 5 years of follow-up. METHODS: Case report. RESULTS: A 23-year-old woman presented with bilateral progressive keratoconus and received CXL treatment (Dresden protocol) for both eyes in March 2009. The patient has demonstrated gradual significant corneal thinning (from a preoperative value of 464 µm to 243 µm) and progressive flattening (+11.1-diopter change in spherical equivalent) in her right eye, over a 5-year period. The fellow eye remained stable during the same postoperative period. CONCLUSIONS: This is the first case report of significant progressive corneal flattening and thinning after undergoing CXL treatment for progressive keratoconus.

Safety of high-intensity corneal collagen crosslinking.

PURPOSE: To evaluate the safety of a new high-intensity corneal collagen crosslinking (CXL) treatment protocol for keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective interventional case series. METHODS: Patients with progressive keratoconus had CXL using a new treatment protocol with 9 mW/cm(2) irradiance for duration of 10 minutes. The rate of reepithelialization, endothelial cell density (ECD), corrected distance visual acuity (CDVA), and steep and flat keratometry (K) values were evaluated preoperatively and 3 months postoperatively. RESULTS: Nine patients (10 eyes) were enrolled. No intraoperative or early postoperative complications were observed in any patient. The ECD did not change significantly 3 months postoperatively (P=.169). The CDVA improved from 0.19 logMAR ± 0.20 (SD) preoperatively to 0.10 ± 0.16 logMAR 3 months postoperatively; however, the improvement did not attain significance (P=.141). No eye lost lines of CDVA. The mean steep K readings decreased significantly from 48.04 ± 2.57 diopters (D) preoperatively to 46.51 ± 2.81 D 3 months postoperatively (P=.047); the mean flat K readings did not change significantly postoperatively (P=.285). CONCLUSIONS: Corneal collagen crosslinking at 9 mW/cm(2) irradiance for 10 minutes did not cause significant changes in ECD or intraoperative or early postoperative complications. None patient lost a line of CDVA 3 months after the procedure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Long-term results of combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for keratoconus: Cretan protocol.

PURPOSE: To present the long-term results of combined transepithelial phototherapeutic keratectomy (PTK) and corneal collagen crosslinking (CXL) for keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective case series. METHODS: Patients with progressive keratoconus had combined transepithelial PTK and CXL (Cretan protocol). Visual and refractive outcomes and the endothelial cell density (ECD) were evaluated preoperatively and postoperatively. RESULTS: Twenty patients (23 eyes) were enrolled; postoperatively 23 eyes were evaluated at 1 and 2 years, 11 at 3 years, and 7 at 4 years. The mean follow-up was 33.83 months±10.82 (SD) (range 24 to 56 months). No intraoperative or postoperative complications occurred. The mean uncorrected distance visual acuity improved significantly from 0.99±0.57 logMAR preoperatively to 0.61±0.36 logMAR at the last follow-up (P<.001) and the mean corrected distance visual acuity, from 0.27±0.24 logMAR to 0.17±0.14 logMAR (P=.018), respectively. The mean steep and mean flat keratometry readings decreased significantly from 53.39±7.14 diopters (D) and 47.17±4.87 D, respectively, preoperatively to 49.99±4.36 D (P<.001) and 45.47±2.95 D (P=.002), respectively, at the last follow-up. The mean corneal astigmatism improved significantly from -6.27±4.19 D preoperatively to -4.52±2.80 D (P<.001) at the last follow-up. No significant ECD alterations occurred (P>.05). CONCLUSION: Combined transepithelial PTK and CXL was effective and safe in keratoconic patients over a long-term follow-up. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Corneal collagen crosslinking failure in a patient with floppy eyelid syndrome.

UNLABELLED: A 30-year-old man with bilateral floppy eyelid syndrome (more prominent in the left eye) and progressive keratoconus had corneal collagen crosslinking (CXL) in both eyes. No intraoperative or early postoperative complications were found. Topographic examination after CXL revealed a continuous increase in the keratometric values in the left eye in which the floppy eyelid syndrome was more prominent, indicating keratoconus progression (CXL failure). The fellow eye with the less prominent floppy eyelid syndrome remained stable during the follow-up period. Floppy eyelid syndrome could be a risk factor for CXL failure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Long-term follow-up of corneal collagen cross-linking for keratoconus--the Cretan study.

PURPOSE: The aim of this study was to present the long-term results of corneal collagen cross-linking (CXL) in patients with keratoconus. METHODS: In this prospective, interventional case series, patients with progressive keratoconus underwent CXL treatment according to the Dresden protocol. Visual, refractive, and topographic outcomes along with endothelial cell density were evaluated preoperatively and at 1, 2, 3, 4, and 5 years postoperatively. RESULTS: Twenty-one patients (25 eyes) were enrolled. The mean follow-up was 43.7 ± 12.2 (range, 24-60) months. Logarithm of the minimum angle of resolution (logMAR) mean uncorrected visual acuity and the mean best spectacle-corrected visual acuity improved significantly from 0.92 ± 0.54 and 0.29 ± 0.21 preoperatively to 0.63 ± 0.41 (P = 0.010) and 0.18 ± 0.18 (P = 0.011), respectively, at the last follow-up. Mean steep and mean flat keratometry readings reduced significantly from 52.53 ± 6.95 diopters (D) and 48.11 ± 5.98 D preoperatively to 49.10 ± 4.50 D (P < 0.001) and 45.58 ± 3.81 D (P = 0.001), respectively, at the last follow-up. The mean endothelial cell density was 2708 ± 302 cells per square millimeter preoperatively and did not change significantly (P > 0.05) at any postoperative interval (2593 ± 258 cells/mm at the last follow-up; P = 0.149). CONCLUSIONS: CXL seems to be effective and safe in halting progression of keratoconus over a long-term follow-up period up to 5 years postoperatively.