Accelerated Corneal Crosslinking to Arrest Progression of Corneal Ectasia: A Prospective Multicenter Study.

OBJECTIVES: To report the results of epithelium-off accelerated corneal collagen crosslinking (accelerated corneal crosslinking [ACXL]) in patients with progressive keratoconus. METHODS: This prospective, nonrandomized, noncomparative, interventional, multicenter clinical study included all patients who underwent ACXL, either continuous (c-ACXL; 9 mW/cm 2 , 10', 5.4 J/cm 2 ) or pulsed (p-ACXL; 2″ON/1″OFF, 30 mW/cm 2 , 4.5', 5.4 J/cm 2 ) between January 2014 and May 2017. Best-corrected visual acuity, sphere, cylinder, spherical equivalent, and topographical keratometry data were collected preoperatively and at 1, 3, 6, 12, 18, and 24 months postoperatively. RESULTS: Ninety-six eyes of 78 patients were included. The mean age was 20.8±4.4 years (14-33) for c-ACXL and 26.7±7.7 years (12-37) for p-ACXL. The mean best-corrected visual acuity was 0.4±0.4 for c-ACXL and 0.01±0.1 for p-ACXL preoperatively, and 0.3±0.3 ( P =0.0014) and -0.01±0.1 ( P =0.1554), respectively, at the last follow-up. The subjective sphere and spherical equivalent did not show statistically significant differences between the time points ( P >0.05). The subjective cylinder showed significant differences ( P =0.0013 for c-ACXL; P =0.0358 for p-ACXL). Keratometric values (K steep , K flat , and SimK) remained stable, with no statistically significant differences ( P >0.05). No major complications were noted. CONCLUSIONS: Both c-ACXL and p-ACXL are equally safe and effective ACXL protocols in stabilizing the progression of keratoconus and can be considered alternatives to the conventional Dresden protocol.

[Optic neuritis: diagnosis, treatment and clinical implications]. / Névrite du nerf optique: diagnostic, traitement et implications cliniques.

Optic neuritis is one of the most important causes of visual loss in young and middle aged adults. The prognosis in terms of functional outcome is good. The diagnosis of optic neuritis is a clinical one. Steroids can shorten the recovery time but do not change the long term functional outcome. The MRI is the most important investiga- tion to assess an associated risk of multiple sclerosis. Optic cohe- rence tomography (OCT) contribute additional details to course and functional outcome of optic neuritis. In the future the OCT may additionally contribute to the relationship between optic neuritis and possible associated multiple sclerosis.

Additive effect of repeated corneal collagen cross-linking in keratoconus.

PURPOSE: To report the long-term clinical outcome in a patient diagnosed as having bilateral progressive keratoconus who received a single corneal collagen cross-linking (CXL) treatment in the right eye and repeated CXL in the left eye. METHODS: Observational case report. Topographical changes were assessed by high-resolution Scheimpflug imaging. The right eye underwent a standard epithelium-off CXL procedure in February 2008, followed by the left eye 4 weeks later. In 2012, the left eye was treated with CXL for a second time. Irradiation was performed in all cases at a fluence of 5.4 J/cm². Energy settings were 30 minutes @ 3 mW/cm² for the CXL procedures performed in 2008, and 10 minutes @ 9 mW/cm² for the second CXL procedure of the left eye that was performed in 2012. RESULTS: The right eye that underwent a single CXL procedure showed a flattening of keratometry values between 2008 and 2012, followed by stabilization. The left eye showed a similar flattening effect between 2008 and 2012, followed by another flattening effect after the second CXL procedure and accompanied by a distinct increase in corrected distance visual acuity. CONCLUSIONS: Following repeated CXL, the corneal stroma and endothelium remained inconspicuous, and postoperative haze and visibility of the stromal demarcation line was similar to what is usually observed after a single CXL procedure. Whether the additive flattening effect of the anterior surface observed in this single case goes along with an additive increase in biomechanical stiffness remains to be seen.

Accelerated photoactivated chromophore for keratitis-corneal collagen cross-linking as a first-line and sole treatment in early fungal keratitis.

PURPOSE: To report the use of accelerated photoactivated chromophore for keratitis-corneal collagen cross-linking (PACK-CXL) as a first-line treatment in a patient with an atypical fungal keratitis. METHODS: Case report and literature review. RESULTS: A patient who presented with a painful peripheral corneal infiltrate underwent PACK-CXL with a local limited abrasion and accelerated ultraviolet-A irradiation at 365 µm and 9 mW/cm² for 10 minutes. Cultures grew Aureobasidium pullulans. The corneal epithelium closed completely within 3 days and the infiltrate was completely eradicated without administration of antibiotics. CONCLUSIONS: Accelerated PACK-CXL was successfully used as a first-line and sole treatment in a case of early fungal keratitis caused by Aureobasidium pullulans. Further characterization of the antifungal effect of PACK-CXL is needed in prospective studies.

Antibacterial efficacy of accelerated photoactivated chromophore for keratitis-corneal collagen cross-linking (PACK-CXL).

PURPOSE: To investigate whether optimized photoactivated chromophore for keratitis-corneal collagen cross-linking (PACK-CXL) treatment settings allow accelerating treatment while maintaining antibacterial efficacy. METHODS: Staphylococcus aureus and Pseudomonas aeruginosa strains were irradiated with ultraviolet-A light of equal fluence but different intensity settings (18 mW/cm² for 5 minutes and 36 mW/cm² for 2.5 minutes). The killing rate was determined by comparing the number of colony-forming units between cross-linked specimens and non-irradiated controls. The potential additional effect of 0.001% benzalkonium chloride was also investigated. RESULTS: The killing rates for Staphylococcus aureus were 92.5% ± 5.5% (5 minutes at 18 mW/cm²) and 94.4% ± 2.9% (2.5 minutes at 36 mW/cm²). For Pseudomonas aeruginosa, the killing rates were 93.2% ± 8.3% (5 minutes at 18 mW/cm²) and 92.9% ± 5.0% (2.5 minutes at 36 mW/cm²). The presence of benzalkonium chloride in the riboflavin solution did not increase the killing rate significantly. CONCLUSIONS: The antibacterial efficacy of PACK-CXL follows the Bunsen-Roscoe law of reciprocity and can be maintained even when the irradiation intensity is considerably increased. These optimized settings may allow a shortened treatment time in the future for PACK-CXL and thus help facilitate the transition from the operating room to the slit lamp for treatment.

[Keratoconus treatment by corneal cross-linking (CLX)]. / Prise en charge du kératocône par cross-linking du collagène cornéen.

Keratoconus is a disease of the cornea that usually begins during puberty and progressively weakens its biomechanical structure. Keratoconic eyes show a conic shape and progressive thinning, both leading to irregular astigmatism and reduced vision that cannot be corrected by glasses. In early cases, special contact lens can partly compensate for the visual loss while they do not stop disease progression. Until recently, the only treatment option was a corneal transplant. In 1999, a technique called corneal collagen cross-linking (CXL) was used in human corneas suffering from keratoconus for the first time. CXL uses a process called photopolymerization to halt the progression of keratoconus with an efficacy of more than 95%. Today our challenge is to screen and identify patients early enough to offer a treatment on time before irreversible vision loss develops.

Using corneal graft from keratoconic donor for lamellar and penetrating keratoplasties.

We report the use of two corneal grafts derived from a donor, with a history of early stage keratoconus, for lamellar and penetrating keratoplasty. The first graft was used to perform Descemet stripping automated endothelial keratoplasty (DSAEK) in a patient with endothelial dysfunction and advanced pseudoexfoliative glaucoma. The second graft was used for an emergency penetrating keratoplasty in a patient with corneal perforation secondary to uncontrolled herpes keratitis. In the first case, 1 year postoperatively, the graft was clear and attached with no signs of rejection or failure. In the second case, the perforation did not relapse after keratoplasty and the globe retained its structural integrity during the 1-year follow-up.

Contact Transscleral Cyclodiode Laser Treatment for Refractory Glaucoma After Penetrating Keratoplasty: Retrospective Long-term Outcomes.

PRéCIS:: This is a retrospective study with long-term follow-up using transscleral cyclodiode laser photocoagulation (TCP) with low complication rate and good graft survival and intraocular pressure (IOP) control. Selective 180-degree TCP may offer a good IOP control with reduced complication rates. PURPOSE: To study the long-term safety and efficacy of contact TCP in eyes with refractory glaucoma after penetrating keratoplasty (PKP). PATIENTS AND METHODS: All consecutive patients who were treated with TCP for refractory glaucoma following PKP between March 1996 and February 2017 in a tertiary corneal transplantation service in the United Kingdom. Only patients with a follow-up of 5 years were included. Eligible patients were identified through the corneal transplantation service database. Medical records and database data were retrospectively analyzed and compared at 5 years from baseline. RESULTS: In total, 28 eyes of 28 patients presented with a mean IOP of 30.4 mm Hg (SD, 7.5) at baseline despite maximally tolerated topical and systemic antiglaucoma medications. IOP was reduced significantly to 12.8 mm Hg (SD, 3.6) (P<0.0001) at 5 years with 100% of patients with a successfully controlled IOP (defined as ≤21 mm Hg). All patients had a clear graft at the beginning of the study period and at 5 years 60.7% (n=17) still presented clear grafts. The average number of topical glaucoma medication was reduced from 2.8 (SD, 0.8) to 1.7 (SD, 1.2) (P=0.019) at 5 years. Visual acuity remained stable in 67.9% of patients at 5-year endpoint. No complications (ie, hypotony or phthisis bulbi) were reported during the study period and the corneal graft failure rate remained low at 5 years (39.3%). CONCLUSIONS: Cyclodiode laser treatment with initial selective 180-degree protocol seems to be an efficient therapeutic option in the management of patients with refractory glaucoma post-PKP when compared with other surgical alternatives. A selective 180-degree protocol seems to potentially reduce the rate of complications. Further randomized controlled studies are needed to compare outcomes with modified treatment's protocols and glaucoma drainage device.

Combined Corneal Wedge Resection And Corneal Cross-Linking For Pellucid Marginal Degeneration: A First Report.

BACKGROUND: Advanced pellucid marginal degeneration is a debilitating disease that warrants the use of surgery when the visual acuity is reduced and contact lenses are not tolerated anymore. It is traditionally managed with corneal transplantation, however alternative surgical options exist. Corneal wedge resection allows for good visual rehabilitation without the risks of tissue rejection. However topographical and refractive results are in some instance fluctuating. We present here the use of corneal cross-linking in order to stabilize the parameters on the long term. CASE PRESENTATION: We present here the case of a 53 years old patient with bilateral advanced pellucid marginal degeneration. As he is now intolerant to contact lenses a surgical option is offered to him. In order to avoid using donated tissue through corneal grafting we decide to perform a sectorial lamellar crescentric wedge excision of the thinner inferior part of the cornea involving the pellucid marginal degeneration and suture it. The first eye shows initial good results however after few months regression is observed. The second eye is then treated with the same surgical technique combined with cornea cross-linking. Long-term follow-up shows stabilization and absence of regression in the second eye up to eight months after the surgery. CONCLUSION: Combining corneal cross-linking with corneal wedge resection in the case of advanced pellucid marginal degeneration patients could be a good option in order to stabilize topographical and refractive results and reduces the risk of regression.

Nepafenac Ophthalmic Suspension 0.3% for the Management of Ocular Pain After Photorefractive Keratectomy.

PURPOSE: To investigate the effect of nepafenac 0.3% in a once daily dosage regarding pain and healing after photorefractive keratectomy (PRK). METHODS: This was a prospective, comparative, contralateral randomized study of 35 patients undergoing PRK for the correction of low to moderate myopia and myopic astigmatism. After randomization, patients received nepafenac 0.3% ophthalmic suspension once daily in one eye (nepafenac 0.3% group) and nepafenac 0.1% ophthalmic suspension three times a day in the other eye (nepafenac 0.1% group) until the second postoperative day. Pain was evaluated every 2 hours on the day of the operation and then once daily using a scale ranging from 0 to 4. Patients were then examined at 2 weeks and 1, 3, 6, and 12 postoperative months. Visual acuity and subepithelial haze were also assessed. RESULTS: No differences were detected between groups in pain scores, subepithelial haze scores, or visual acuity. Refractive predictability was also similar. CONCLUSIONS: Nepafenac 0.3% ophthalmic suspension in a daily regimen after PRK seems to be an effective treatment for pain and ocular discomfort with effects similar to the 0.1% suspension. [J Refract Surg. 2018;34(3):171-176.].

Uneventful Anterior Migration of Intravitreal Ozurdex Implant in a Patient with Iris-Sutured Intraocular Lens and Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: We report here the case of a patient with anterior segment migration of intravitreal dexamethasone implant as well as its management and outcome. METHODS: The patient had the following sequence of events: complicated cataract surgery, iris-sutured intraocular lens implant, followed by cystoid macular edema treated with intravitreal Avastin, retinal vein occlusion treated with intravitreal dexamethasone implant, corneal decompensation treated with Descemet stripping automated endothelial keratoplasty (DSAEK), and finally recurrence of macular edema treated with repeated intravitreal dexamethasone implant. RESULTS: Dexamethasone implant had completely dissolved from the eye 12 weeks after insertion without any complication. CONCLUSION: A conservative approach with regular monitoring in the situation of a quiet anterior segment without any corneal decompensation can provide enough time for the implant to dissolve without causing any complication to the involved eye, avoiding any additional surgical intervention, as presented in this case report. Despite the fact that the implant was left for natural dissolution, there were no adverse effects related to the graft or the eye.

Corneal Scarring and Hyperopic Shift After Corneal Cross-linking for Corneal Ectasia After SMILE.

PURPOSE: To report a case of severe corneal scarring and hyperopic shift after corneal cross-linking (CXL) for the treatment of ectasia following small incision lenticule extraction (SMILE). METHODS: Case report and literature review. RESULTS: A 35-year-old man was referred with severe unilateral corneal haze that developed after CXL. The patient had undergone SMILE 4 years earlier in both eyes. Nineteen months postoperatively, the patient presented with bilateral decrease in vision and corneal topography revealed corneal ectasia in the right eye. CXL was performed in the right eye and a deep stromal haze was observed 1 year later. Comparative maps showed progressive corneal thinning with corresponding flattening that induced hypermetropization and astigmatism. CONCLUSIONS: CXL after SMILE in this original case resulted in severe deep corneal haze and corneal flattening with hyperopic shift. [J Refract Surg. 2018;34(11):779-782.].

Repeated Cross-linking After a Short Time Does Not Provide Any Additional Biomechanical Stiffness in the Mouse Cornea In Vivo.

PURPOSE: To study whether repeated collagen cross-linking (CXL) performed in vivo in mice shows an additive effect on mechanical corneal stiffness. METHODS: In this experimental study, epithelium-off CXL was performed in a total of 18 eyes from male C57BL/6 mice, with 0.27%-riboflavin solution applied for 20 minutes, followed by ultraviolet-A (UVA) irradiation (365 nm, 9mW/cm2) for 2:50 minutes (fluence 1.53 J/cm2). CXL was performed as either a single (1×CXL) or a repeated (2×CXL) treatment. Un-irradiated corneas served as controls. In the 2×CXL group, the procedure was performed on day 1 and day 4 to ensure complete reepithelialization between sessions. Biomechanical analysis was performed on day 7. Corneas were harvested with a small scleral ring and mounted on a customized two-dimensional flap holder. The biomechanical measurement consisted of three parts: (1) pre-conditioned during three cycles from 0.04 to 0.4 N, (2) stress relaxation during 120 seconds following 0.4 N force application, and (3) stress-strain curve until break. RESULTS: After the relaxation period of 120 seconds, highly significant differences (P < .001) were found between the controls and both 1×CXL corneas and 2×CXL corneas. No significant difference (P = .70) was detected between the 1×CXL and 2×CXL groups. The stress remaining after relaxation was 355 ± 25.2 kPa in the control group, 457 ± 34.1 kPa in the 1×CXL group, and 463 ± 22.2 kPa in the 2×CXL group. No significant differences in the stress-strain curves were found between the conditions. CONCLUSIONS: Repeated CXL 3 days after the first procedure does not further increase corneal stiffness in mice in vivo. [J Refract Surg. 2017;33(1):56-60.].

Pregnancy-induced Changes in Corneal Biomechanics and Topography Are Thyroid Hormone Related.

PURPOSE: To identify biomechanical and topographic changes of the cornea during pregnancy and the postpartum period and its association to hormonal changes. DESIGN: Prospective single-center observational cohort study. METHODS: Participants were 24 pregnant women (48 eyes), monitored throughout pregnancy and after delivery. Biomechanical and topographic corneal properties were measured using the Ocular Response Analyzer (ORA) and a Scheimpflug imaging system (Pentacam HR) each trimester and 1 month after delivery. At the same consultations blood plasma levels of estradiol (E2) and thyroid hormones (TSH, T3t, T4t) were also determined. A factorial MANCOVA was used to detect interactions between hormonal plasma levels and ocular parameters. RESULTS: Significant differences in corneal biomechanical and topographic parameters were found during pregnancy in relation to T3t (p = .01), T4t (p < .001), T3t/T4t (P = .001), and TSH (p = .001) plasma levels. E2 plasma levels (p = .092) and time period of measurement (p = .975) did not significantly affect corneal parameters. TSH levels significantly affected the maximal keratometry reading (p = .036), the vertical keratometry reading (p = .04), and the index of height asymmetry (p = .014). Those results persist after excluding hypothyroidism patients from the statistical analysis. CONCLUSIONS: Hormonal changes affecting corneal biomechanics and topography during pregnancy could be thyroid related. Dysthyroidism may directly influence corneal biomechanics and represents a clinically relevant factor that needs further investigation.

PACK-CXL: Corneal cross-linking in infectious keratitis.

BACKGROUND: Corneal cross-linking (CXL) using ultraviolet light-A (UV-A) and riboflavin is a technique developed in the 1990's to treat corneal ectatic disorders such as keratoconus. It soon became the new gold standard in multiple countries around the world to halt the progression of this disorder, with good long-term outcomes in keratometry reading and visual acuity. The original Dresden treatment protocol was also later on used to stabilize iatrogenic corneal ectasia appearing after laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). CXL efficiently strengthened the cornea but was also shown to kill most of the keratocytes within the corneal stroma, later on repopulated by those cells. REVIEW: Ultraviolet-light has long been known for its microbicidal effect, and thus CXL postulated to be able to sterilize the cornea from infectious pathogens. This cytotoxic effect led to the first clinical trials using CXL to treat advanced infectious melting corneal keratitis. Patients treated with this technique showed, in the majority of cases, a stabilization of the melting process and were able to avoid emergent à chaud keratoplasty. Following those primary favorable results, CXL was used to treat beginning bacterial keratitis as a first-line treatment without any adjunctive antibiotics with positive results for most patients. In order to distinguish the use of CXL for infectious keratitis treatment from its use for corneal ectatic disorders, a new term was proposed at the 9th CXL congress in Dublin to rename its use in infections as photoactivated chromophore for infectious keratitis -corneal collagen cross-linking (PACK-CXL). CONCLUSION: PACK-CXL is now more frequently used to treat infections from various infectious origins. The original Dresden protocol is still used for this purpose. Careful modifications of this protocol could improve the efficiency of this technique in specific clinical situations regarding certain types of pathogens.

PACK-CXL: Corneal Cross-linking for Treatment of Infectious Keratitis.

This article discusses corneal cross-linking (CXL) and how it transitioned from a modality for treating corneal ectatic disorders to an inventive means of treating infectious keratitis. Initially, CXL was successfully developed to halt the progression of ectatic diseases such as keratoconus, using the standard Dresden protocol. Later, indications were extended to treat iatrogenic ectasia developing after laser-assisted in situ keratomileusis (LASIK) and photo-refractive keratectomy (PRK). At the time, it had been postulated that the combination of ultraviolet light with riboflavin could not only biomechanically strengthen the cornea but also was capable of destroying living cells and organisms including keratocytes and pathogens. Thus a new and innovative concept of treatment for infectious keratitis emerged through the use of CXL technology. Initially only advanced infectious melting ulcers resisting standard microbicidal therapy were treated with CXL in addition to standard therapy. In subsequent studies CXL was also used to treat bacterial keratitis as first line therapy without the use of concomitant antibiotic therapy. With the increasing interest in CXL technology to treat infectious keratitis and to clearly separate its use from the treatment of ectatic disorders, a new term was adopted at the 9(th) CXL congress in Dublin for this specific indication: PACK-CXL (photoactivated chromophore for infectious keratitis). PACK-CXL has the potential to eventually become an interesting alternative to standard antibiotic therapy in treating infectious corneal disorders, and may help reduce the global burden of microbial resistance to antibiotics and other therapeutic agents.

Misdirected aqueous flow in rhegmatogenous retinal detachment: a pathophysiology update.

It is widely accepted that the origin of subretinal fluid in rhegmatogenous retinal detachment (RRD) is liquid vitreous and that posterior vitreous detachment (PVD) and associated retinal tears are caused by vitreoretinal traction from intra-ocular currents, contraction of collagen fibers, and gravity. These explanations, however, are incomplete. We present a new synthesis of experimental and clinical evidence, updating understanding of fundamental pathophysiological processes in RRD. Misdirected aqueous flow is shown to more convincingly explain the origin of subretinal fluid in clinical RRD, to be the most likely cause of acute PVD and retinal tear formation, and also to contribute to initial detachment of the retina at retinal tears. Misdirected aqueous flow in RRD is a pathophysiological process, rather than the "aqueous misdirection syndrome", and occurs without visible anterior chamber shallowing or acute glaucoma.

Increased Biomechanical Efficacy of Corneal Cross-linking in Thin Corneas Due to Higher Oxygen Availability.

PURPOSE: To compare the currently available ultraviolet-A (UV-A) corneal cross-linking (CXL) treatment protocols for thin corneas with respect to oxygen, UV fluence, and osmotic pressure. METHODS: Freshly enucleated murine (n = 16) and porcine (n = 16) eyes were used. The dependency on oxygen and the amount of UV absorption were evaluated using different CXL protocols, including standard CXL, contact lens-assisted CXL (caCXL), and CXL after corneal swelling. The CXL protocol was adapted from the treatment parameters of the human cornea to fit the thickness of murine and porcine corneas. Immediately after CXL, the corneas were subjected to biomechanical testing, including preconditioning, stress relaxation at 0.6 MPa, and stress-strain extensiometry. A two-element Prony series was fitted to the relaxation curves for viscoelastic characterization. RESULTS: Standard CXL was most efficient; prior corneal swelling reduced the long-term modulus by 6% and caCXL by 15% to 20%. Oxygen reduction decreased the long-term modulus G∞ by 14% to 15% and the instantaneous modulus G0 by 2% to 5%, and increased the short-term modulus G2 by 22% to 31%. Reducing the amount of absorbed UV energy decreased the long-term modulus G∞ by 5% to 34%, the instantaneous modulus G0 by 7% to 29%, and the short-term modulus G2 by 17% to 20%. The amount of absorbed UV light was more important in porcine than in murine corneas. CONCLUSIONS: The higher oxygen availability in thin corneas potentially increases the overall efficacy of riboflavin UV-A CXL compared to corneas of standard thickness. Clinical protocols for thin corneas should be revised to implement these findings.