Faculty Bibliography

PURPOSE/UNASSIGNED:To assess corneal resistance to enzymatic digestion after rose bengal (RB)/green light and RB/green light followed by riboflavin (RF)/ultraviolet A (UV-A) cross-linking (CXL), with or without oxygen. METHODS/UNASSIGNED:Ex vivo porcine corneal buttons (n = 144) underwent CXL with RB/green or RB/green-RF/UV-A under atmospheric 21% oxygen conditions or in a nitrogen chamber with 0.1% oxygen (hypoxic conditions) to test 10- and 15-J/cm2 fluences. After CXL, corneas were digested with 0.3% collagenase A, and mean digestion times (MDTs) were recorded. RESULTS/UNASSIGNED:For the non-irradiated control group, the MDT was 19.75 ± 1.34 hours. Under atmospheric oxygen conditions, RB/green CXL yielded MDTs of 33.69 ± 1.4 and 34.38 ± 1.31 hours with fluences of 10 and 15 J/cm2, respectively. RB/green + RF/UV-A showed MDTs of 39.56 ± 1.93 and 51.94 ± 4.2 hours for combined fluences of 10 + 10 J/cm2 and 15 + 15 J/cm2, respectively. Hypoxic RB/green MDTs were 33.88 ± 1.02 and 34.06 ± 1.57 hours, and RB/green + RF/UV-A MDTs were 39.62 ± 2.5 and 50.35 ± 1.59 hours for the same respective fluences. No significant differences were observed between the control groups and corresponding intervention groups (all P > 0.05). CONCLUSIONS/UNASSIGNED:CXL via RB/green and RB/green-RF/UV-A significantly enhanced corneal collagenase digestion resistance, irrespective of oxygen presence. These findings could help optimize infectious keratitis therapy CXL protocols. TRANSLATIONAL RELEVANCE/UNASSIGNED:Our findings aid the understanding of the molecular mechanisms underlying the therapeutic effect of CXL and may contribute to refining accelerated PACK-CXL protocols and other CXL treatment strategies.

PURPOSE/OBJECTIVE:To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking. METHODS:Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022-January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively. RESULTS:20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from -6.79 ± 4.9 diopter (D) and -4.25 ± 1.8 D to -1.88 ± 2.9 D (P < 0.001) and -2.64 ± 1.4 D (P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D (P < 0.001) and 1 μm (P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively (P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months. CONCLUSIONS:The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management.

PURPOSE/OBJECTIVE:To investigate the light transmission (LT) of UV-A and green light through infected corneas saturated with riboflavin or rose bengal in an ex vivo porcine model for infectious keratitis. SETTING/METHODS:University of Zurich and EMPA. DESIGN/METHODS:Laboratory study. METHODS:Ex vivo porcine eyes (n=162) were divided into three groups: control eyes, eyes infected with Staphylococcus aureus, and eyes infected with Pseudomonas aeruginosa. Corneas remained either uninfected, or were infected with S. aureus, and P. aeruginosa, respectively, and were either left untreated, or were instilled with 0.1% riboflavin or 0.1% rose bengal. Corneal buttons were prepared, and corneal LT was measured at 365 nm and 522 nm using a spectrophotometer. LTs were calculated and compared. Transmission electron microscopy (TEM) was used to visualize structural damage and bacteria within infected corneas. RESULTS:Riboflavin-saturated corneas infected by S. aureus or P. aeruginosa (LT = 0.77% [0.41-1.87] and 0.81% [0.23, 1.46]) exhibited 3.18-fold and 3.02-fold lower LTs than uninfected corneas (LT = 2.45% [2.15, 5.89]) (both p-values < 0.001). No LT difference was found between rose bengal-saturated corneas infected by S. aureus or P. aeruginosa and uninfected corneas (all LTs = 0.01% [0.01-0.01]; both p-values = 0.08). TEM showed bacteria on corneal stroma borders and occasionally inside the stroma. CONCLUSION/CONCLUSIONS:Our results indicate that the amount of light arriving at the corneal endothelium is substantially reduced in infected corneas. The total fluence of clinical PACK-CXL protocols can be safely increased substantially while maintaining a low risk of corneal endothelial damage.

BACKGROUND:Acanthamoeba keratitis (AK) is the most challenging corneal infection to treat, with conventional therapies often proving ineffective. While photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) with riboflavin/UV-A has shown success in treating bacterial and fungal keratitis, and PACK-CXL with rose bengal/green light has demonstrated promise in fungal keratitis, neither approach has been shown to effectively eradicate AK. This case study explores a novel combined same-session treatment approach using both riboflavin/UV-A and rose bengal/green light in a single procedure. CASE PRESENTATION/METHODS:) in a single setting. The procedure was repeated twice due to persistent signs of inflammation and infection. After three combined same-session PACK-CXL treatments, the patient's cornea converted to a quiescent scar, and symptoms of ocular pain, photophobia, epiphora, and blepharospasm resolved. Confocal microscopy revealed no detectable Acanthamoeba cysts. The patient currently awaits penetrating keratoplasty. CONCLUSIONS:The same-session combination of riboflavin/UV-A and rose bengal/green light PACK-CXL effectively treated a patient with confirmed AK that was resistant to conventional medical therapy, suggesting that using two chromophores in a single procedure may represent a future treatment alternative for AK.

Corneal cross-linking (CXL) has profoundly changed the management of keratoconus and other ectatic corneal diseases. Introduced in the late 1990s, CXL marked the first effective intervention to halt disease progression. This chapter describes the history of CXL, beginning with its conceptual foundations and preclinical studies conducted at the University of Dresden. Early experiments established the efficacy of riboflavin and UV-A light to induce collagen cross-linking, which improved corneal stiffness. Clinical translation followed with the Dresden protocol, demonstrating safety and efficacy. Long-term studies confirm sustained benefits, with advances in accelerated protocols and modifications for thin corneas extending eligibility to more patients. Additionally, CXL has expanded into infectious keratitis treatment and refractive surgery. Emerging innovations, such as customized and two-photon CXL, promise further applications. By examining the milestones in its evolution, this paper highlights the transformative impact of CXL on corneal disease management.

PURPOSE/UNASSIGNED:This is a case report of a 31-year-old male patient presenting progressive and markedly asymmetric keratoconus treated with sequential intracorneal ring segment (ICRS) implantation followed by accelerated corneal cross-linking (CXL). OBSERVATIONS/UNASSIGNED:post-CXL) was 19.1 D. CONCLUSIONS AND IMPORTANCE/UNASSIGNED:This original case reports how CXL followed by ICRS implant may result in an early and extreme corneal remodeling. Moreover, such an unusual combination of extreme corneal flattening, thinning, and opacification may imitate a clinical manifestation of central toxic keratopathy and suggests that eyes with ICRS implantation must be followed closely if CXL is performed sequentially after.

Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed.

PURPOSE/UNASSIGNED:The purpose of this study was to determine if concurrent riboflavin/UV-A light (RF/UV-A) and rose Bengal/green light (RB/green) epi-off PACK-CXL enhances corneal resistance to enzymatic digestion compared to separate chromophore/light treatments. METHODS/UNASSIGNED:Ex vivo porcine corneas were allocated as follows. Group A corneas were soaked with riboflavin (RF) and were either not irradiated (A1, controls) or were irradiated with 10 (A2) or 15 J/cm² (A3) UV-A light at 365 nm, respectively. Group B corneas were soaked with RB and either not irradiated (B1, controls) or were illuminated with 10 (B2) or 15 J/cm² (B3) green light at 525 nm, respectively. Corneas in group C were soaked with both RF and RB and were either not irradiated (C1, controls) or were subjected to the same session consecutive 10 J/cm2 (C2) or 15 J/cm2 (C3) UV-A and green light exposure. Following treatment, all corneas were exposed to 0.3% collagenase A to assess digestion time until corneal button dissolution. RESULTS/UNASSIGNED:A1 to A3 digestion times were 21.38, 30.5, and 32.25 hours, respectively, with A2 and A3 showing increased resistance to A1. B1-3 had digestion times of 31.2, 33.81, and 34.38 hours, with B3 resisting more than B1. C1 to C3 times were 33.47, 39.81, and 51.94 hours; C3 exhibited superior resistance to C1 and C2 (both P < 0.05). CONCLUSIONS/UNASSIGNED:Same-session combined RF/UV-A and RB/green PACK-cross-linking significantly increases corneal enzymatic digestion resistance over standalone treatments. TRANSLATIONAL RELEVANCE/UNASSIGNED:Combining RF-based and RB-based PACK-CXL considerably increases corneal collagenase digestion resistance, potentially minimizing ulcer size in clinical contexts.

PURPOSE OF REVIEW/OBJECTIVE:The aim of this study was to summarize the recent developments in corneal cross-linking (CXL) and its indications, including corneal ectasias, refractive surgery and infectious keratitis. RECENT FINDINGS/RESULTS:Advances in CXL technology, such as the use of higher-intensity LED ultraviolet (UV) light sources and a better understanding of the UV-riboflavin photochemical reaction, have enabled safer and more effective methods of cross-linking thin and ultra-thin corneas, and more effective accelerated transepithelial/'epi-on' CXL procedures that are beginning to supplant the Dresden protocol as the 'gold standard' CXL method. CXL is also being used in combination with laser surgery, not only to expand the patient base who can receive refractive surgery, but also to help rehabilitate vision in patients with ectasia. CXL, and CXL combined with photorefractive keratectomy (PRK), can result in corneal flattening of 1-2 D, and corneal regularization of 4-5 D, respectively. Finally, photoactivated chromophore for keratitis-corneal cross-linking (PACK-CXL) has been shown to be an effective therapy for infectious keratitis, both alone, and in combination with antimicrobial drugs. SUMMARY/CONCLUSIONS:CXL has evolved from a single technique to treat a single corneal ectasia, keratoconus, to several techniques with several indications, spanning a spectrum of corneal ectasias, as well as visual rehabilitation, refractive procedures and infectious keratitis treatment.

The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up.