Evaluation of risk factors for treatment failure in canine patients undergoing photoactivated chromophore for keratitis - corneal cross-linking (PACK-CXL): a retrospective study using additive bayesian network analysis.

BACKGROUND: Infectious keratitis is a common ophthalmic condition in canine patients. Sequelae can include keratomalacia and corneal perforation, a vision threatening outcome. Photoactivated chromophore for keratitis - corneal cross-linking (PACK-CXL) is a non-surgical, adjunctive treatment method for infectious keratitis. The goal of this retrospective, multicenter study was to determine risk factors for treatment failure following PACK-CXL in canine patients suffering from suspected infectious keratitis. Medical records from four veterinary ophthalmology services were reviewed, and information related to patient demographics, ophthalmic findings, the PACK-CXL protocol used, and epithelialization time was collected and analyzed. Due to the potential for intervariable relationships, an additive Bayesian network (ABN) analysis was performed to evaluate these complex relationships. RESULTS: Records for 671 eyes (668 dogs) were included in the analysis. Based on the ABN, in the population included here, patients who underwent an accelerated PACK-CXL protocol were less likely to experience treatment failure versus patients treated with a slow protocol. Mutual dependencies between exposure variables were identified by ABN, which would have been overlooked using classical regression. Corneal re-epithelialization time was shortened following PACK-CXL combined with topical medical therapy compared to PACK-CXL alone. CONCLUSIONS: No risk factors associated with treatment failure were identified in the population included in the present study. Canine patients may benefit from the use of accelerated PACK-CXL protocols, especially when combined with topical antibiotics and anti-collagenolytic therapy. The reasons for this apparent positive impact on treatment outcome remain unclear.

Use of corneal cross-linking beyond keratoconus: a systemic literature review.

PURPOSE: The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review aims to analyze the scientific evidence available for the benefit of cross-linking in the management of ophthalmic diseases other than progressive keratoconus or ectasia induced by corneal refractive procedures. METHODS: A systemic literature review. RESULTS: We reviewed 97 studies. We found that collagen cross-linking can limit the progression of several other corneal ectasias, thus reducing and limiting the need for keratoplasty. Collagen cross-linking also can reduce the refractive power of the cornea and can be considered for a moderate degree of bacterial keratitis or when the organism is unidentified, which is refractive to antibiotics alone. However, the comparative rarity of these procedures has limited the extent of evidence. In fungal, Acanthamoeba, and herpes virus keratitis, the evidence is inconclusive of the safety and efficacy of cross-linking. CONCLUSION: Current clinical data is limited, and laboratory data has not fully correlated with published clinical data.

Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study.

OBJECTIVE: The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK). PATIENTS AND METHODS: This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). RESULTS: Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes. CONCLUSION AND RECOMMENDATION: PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.

Corneal cross-linking guards against infectious keratitis: an experimental model.

BACKGROUND: PACK-CXL (photo-activated chromophore for keratitis-corneal cross-linking) is an alternative option in treatment of corneal infections. It inhibits corneal melting by increasing the stromal resistance, besides the microbicidal effect of photo-activated riboflavin. METHODS: Corneal infection with Pseudomonas aeruginosa and Staph aureus bacteria was induced in 20 eyes of 10 rabbits after 6 weeks of corneal cross-linking in half of the eyes, while the other acted as control group. Clinical and corneal histopathological examination was done to evaluate the extent of inflammation, ulceration, organism penetration, and depth of corneal stromal affection. RESULTS: The control eyes developed severe inflammation compared to the cross-linked eyes. Corneal melting occurred in 6 eyes in the control versus none in cross-linked group. Histopathological examination showed that the inflammation was confined to the superficial part of the stroma with localization of the inflammation in the cross-linked eyes in contrast to the control eyes that showed deep infiltration. CONCLUSION: PACK-CXL provides infection localization through increasing the corneal rigidity and resistance to enzymatic digestion, even in the absence of the riboflavin microbicidal role. So, early PACK-CXL is worth to be considered in the IK treatment algorithm.

The bactericidal effect of two photoactivated chromophore for keratitis-corneal crosslinking protocols (standard vs. accelerated) on bacterial isolates associated with infectious keratitis in companion animals.

BACKGROUND: Bacterial corneal infections are common and potentially blinding diseases in all species. As antibiotic resistance is a growing concern, alternative treatment methods are an important focus of research. Photoactivated chromophore for keratitis-corneal crosslinking (PACK-CXL) is a promising oxygen radical-mediated alternative to antibiotic treatment. The main goal of this study was to assess the anti-bactericidal efficacy on clinical bacterial isolates of the current standard and an accelerated PACK-CXL treatment protocol delivering the same energy dose (5.4 J/cm2). METHODS: Clinical bacterial isolates from 11 dogs, five horses, one cat and one guinea pig were cultured, brought into suspension with 0.1% riboflavin and subsequently irradiated. Irradiation was performed with a 365 nm UVA light source for 30 min at 3mW/cm2 (standard protocol) or for 5 min at 18mW/cm2 (accelerated protocol), respectively. After treatment, the samples were cultured and colony forming units (CFU's) were counted and the weighted average mean of CFU's per µl was calculated. Results were statistically compared between treated and control samples using a linear mixed effects model. RESULTS: Both PACK-CXL protocols demonstrated a significant bactericidal effect on all tested isolates when compared to untreated controls. No efficacy difference between the two PACK-CXL protocols was observed. CONCLUSION: The accelerated PACK-CXL protocol can be recommended for empirical use in the treatment of bacterial corneal infections in veterinary patients while awaiting culture results. This will facilitate immediate treatment, the delivery of higher fluence PACK-CXL treatment within a reasonable time, and minimize the required anesthetic time or even obviate the need for general anesthesia.

Corneal cross-linking (CXL)-A clinical study to evaluate CXL as a treatment in comparison with medical treatment for ulcerative keratitis in horses.

OBJECTIVE: Compare CXL treatment with medical treatment alone in horses with stromal, ulcerative keratitis. ANIMALS STUDIED: 24 horses (24 eyes) with stromal, ulcerative keratitis were included. PROCEDURE: 12 horses were initially treated with CXL, and 12 horses were given conventional medical treatment. Topical medical treatment was added to horses in the CXL group if necessary. Parameters including cytology, microbial growth, time to fluorescein negativity, and time to inhibition of stromal melting were evaluated. RESULTS: After the first day of treatments, a decrease in inflammatory signs and pain from the eye was observed in both groups. Stromal melting ceased within 24 hours regardless of treatment. CXL treatment alone was sufficient in 3 horses with noninfectious, superficial stromal ulcerations. Clinical signs of impaired wound healing were seen after 3-14 days in corneas with suspected or proven bacterial infection treated with CXL only, most likely because of insufficient elimination of bacteria deeper in the corneal stroma or because of re-infection from bacteria in the conjunctiva. The average decrease in stromal ulcer area per day after onset of treatment was almost identical between the groups, and no significant difference in time to fluorescein negativity was found. CONCLUSIONS: We consider CXL a possible useful adjunct treatment of corneal stromal ulcers in horses, especially for melting ulcers and as a potential alternative to prophylactic antibiotic treatment for noninfected stromal ulcers. However, CXL should not be used alone for infected or suspected infected stromal ulcers, because topical antibiotics were required in all horses with proven infectious keratitis.

Corneal Cross-Linking Has No Effect on Matrix Metalloproteinase 9 and 13 Levels During Fungal Keratitis on the Early Stage.

The aim of our study was to investigate matrix metalloproteinases, MMP-9 and MMP-13 levels, in the rabbit model of Fusarium and Candida keratitis treated by corneal cross-linking (PACK-CXL). Rabbit corneas were inoculated with fungal inoculum for keratitis. Each group divided into four subgroups, including un-treated group, PACK-CXL group, voriconazole group and PACK-CXL plus voriconazole group. PACK-CXL was applied with 0.25% riboflavin in accelerated Dresden protocol, and 0.1% voriconazole drops were administered. All corneal buttons excised at tenth day after ophthalmological examination. Fungal cell counts and Scheiber scores were determined in all groups. Corneal tissue MMP mRNA levels were evaluated quantitative reverse transcriptase PCR. The difference in MMP-9 and MMP-13 levels at all groups was not statistically significant (p > 0.05). PACK-CXL with 0.25% riboflavin either alone or combined with antifungal drops was unable to provide decline in inflammatory findings in both macroscopic and microscopic levels similar to medical antifungal treatment.

Fungal Keratitis: Diagnosis, Management, and Recent Advances.

Fungal keratitis is one of the major causes of microbial keratitis that may lead to corneal blindness. Many problems related to diagnosis and therapy are encountered in fungal keratitis, including difficulty in obtaining laboratory diagnoses and the availability and efficacy of antifungal medications. Intensive and prolonged use of antifungal topical preparations may not be enough. The use of antifungal medications is considered the main treatment for fungal keratitis. It is recommended to start antifungal therapy after confirmation of the clinical diagnosis with a smear or positive cultures. Topical application of antifungal medications is a mainstay for the treatment of fungal keratitis; however, systemic, intra-stromal, or intra-cameral routes may be used. Therapeutic keratoplasty is the main surgical procedure approved for the management of fungal keratitis with good success rate. Intrastromal corneal injection of antifungal medications may result in steady-state drug levels within the corneal tissue and prevent intervals of decreased antifungal drug concentration below its therapeutic level. In cases of severe fungal keratitis with deep stromal infiltration not responding to treatment, intracameral injection of antifungal agents may be effective. Collagen cross-linking has been proposed to be beneficial for cases of fungal keratitis as a stand-alone therapy or as an adjunct to antifungal medications. Although collagen cross-linking has been extensively studied in the past few years, its protocol still needs many modifications to optimize UV fluence levels, irradiation time, and concentration of riboflavin to achieve 100% microbial killing.

Photoactivated chromophore-corneal cross-linking accelerates corneal healing in fungal keratitis: an updated meta-analysis.

AIM: To determine the effectiveness and safety of photoactivated chromophore-corneal cross-linking (PACK-CXL) adjuvant in infectious keratitis by April 5, 2022. METHODS: We searched randomized controlled trials (RCTs) comparing standard antibiotic treatment (SAT) plus PACK-CXL to SAT in infectious keratitis in Embase, MEDLINE with PubMed, Web of Science, and Cochrane Library. We independently screened and extracted data using predesigned tables. Cochrane's risk-of-bias tool was utilized to examine the quality of RCTs. A random-effects model was employed to determine the overall effect size of the meta-analyses. Grading of Recommendations, and Assessment, Development and Evaluations (GRADE) was also performed to examine the quality of evidence. RESULTS: Seven eligible RCTs with 283 patients were acquired. Adjuvant PACK-CXL reduced the time needed to perform corneal healing in fungal keratitis (- 1.33 months; 95% CI, - 1.83 to - 0.42, I2 = 0%, P < 0.05) as compared to SAT alone. The risks of adverse events were not significantly different both in fungal and bacterial keratitis. Due to the substantial heterogeneity among studies, such as population, the type and severity of infectious keratitis, drug regimens of SAT, PACK-CXL protocol, and the judgment of subjective outcomes, the evidence grade was low. CONCLUSION: Adjuvant PACK-CXL accelerates fungal keratitis healing as compared to SAT alone. But more rigorous RCTs are required to determine the clinical effectiveness and safety.

Accelerated high fluence photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study.

Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp. Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment. Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3-14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96). Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.

Therapeutic non-ectasia applications of cornea cross-linking.

Corneal cross-linking is a photopolymerization technique traditionally used to strengthen corneal tissue. Corneal cross-linking utilizes riboflavin (vitamin B2) as a photosensitizer and ultraviolet-A light (UVA) to create strong covalent bonds within the corneal stroma, increasing tissue stiffness. Multiple studies have demonstrated corneal cross-linking's effectiveness in treating corneal ectasia, a progressive, degenerative, and non-inflammatory thinning disorder, as quantified by key tomographic, refractive, and visual parameters. Since its introduction two decades ago, corneal cross-linking has surpassed its original application in halting corneal ectatic disease and its application has expanded into several other areas. Corneal cross-linking also possesses antibacterial, antienzymolytic and antioedematous properties, and has since become a tool in treating microbial keratitis, correcting refractive error, preventing iatrogenic ectasia, stabilising bullous keratopathy and controlling post keratoplasty ametropia. This review provides an overview of the current evidence base for the therapeutic non-ectasia applications of cornea cross-linking and looks at future developments in the field.

Photo-activated chromophore for infectious keratitis cross-linking and its efficacy as a treatment modality in managing microbial keratitis.

Purpose: To assess Photo Activated Chromophore for Infective Keratitis-Cross Linking (PACK-CXL) and its efficacy as a treatment modality in managing microbial keratitis. Methods: Single Centre prospective interventional study in infectious keratitis. A total of eleven patients were taken who had corneal thickness (CT) more than 400µm. PACK-CXL was performed according to Dresden's protocol. The response was assessed by slit lamp examination, BCVA and AS-OCT at the time of complete healing. Results: The mean visual acuity at presentation was 1.207logMAR (0.3-3) which improved to mean value of 0.53logMAR (0.3-1). Mean time taken for complete epithelization was 17.45 days (14- 30 days) and that for complete healing was 33.72 days (21- 60 days). Mean CT at the baseline was 650.5± 108µm which reduced on consecutive follow up visits. There was reduction in the symptoms in nine patients except in two. One case reported increase in symptoms with worsening increase in endoexudates and hypopyon, and the other developed drug toxicity due to topical medications. Conclusion: Patients who underwent PACK-CXL showed good and early healing, good remodelling of cornea and improved visual acuity. The recalcitrant cases became responders to the same medications after PACK-CXL. Thus, PACK-CXL works well for both fungal and bacterial keratitis.

Comparison between three different high fluence UVA levels in corneal collagen cross-linking for treatment of experimentally induced fungal keratitis in rabbits.

INTRODUCTION: The aim of this study was to compare the efficacy of Photo-Activated Chromophore for Keratitis - Corneal Collagen Cross-linking (PACK-CXL) of three different total UVA fluence levels and topical voriconazole in treatment of fungal keratitis experimentally induced in rabbits. METHODS: This is an interventional experimental study including both eyes of 16 rabbits (32 eyes). Fungal keratitis was induced by intrastromal injection of Fusarium Solani into the cornea. The rabbits were then divided into four groups (8 eyes for each) from which group A received Voriconazole eye drops and considered as control group. Group B, C, D received single PACK-CXL session with total fluence levels of 7.2, 10.0 and 15.0 J/cm2 for each respectively. Daily clinical examination was recorded and all corneas were removed for microbiology and histopathology on day ten. RESULTS: The mean clinical signs score eyes treated with high fluence PACK-CXL showed evident clinical improvement from fourth to tenth day of treatment. This improvement was equivalent to that of Voriconazole treatment. The results showed better improvement with increasing the UVA total fluence levels but this difference was not statistically significant (P < 0.05). Similarly, the median CFU/ml declined on increasing UVA fluence but with no statistically significant values. Histopathological examination revealed better improvement of inflammatory signs on higher fluence levels compared to lower ones. CONCLUSIONS: High intensity PACK-CXL (30 mW/cm2) was as effective as Voriconazole in the treatment of fungal keratitis in rabbits. Increasing the fluence of UVA was associated with slightly better clinical outcomes with no added risks. More clinical studies are needed to confirm these results.

Treatment of recalcitrant Acanthamoeba Keratitis with Photoactivated Chromophore for Infectious Keratitis Corneal Collagen Cross-Linking (PACK-CXL).

PURPOSE: To describe a case of recalcitrant Acanthamoeba Keratitis (AK) complicated by medical non-compliance and medication intolerance that was successfully treated with photoactivated chromophore for infectious keratitis corneal collagen cross-linking (PACK-CXL). OBSERVATIONS: A 31-year-old male presented with right eye pain and redness in the setting of fresh water exposure and scleral contact lens wear. He had lack of a response to treatment with antiviral therapy for 3 months by an outside provider. Cultures were found to be positive for Acanthamoeba and the patient was treated with an extended course of various anti-amoebic therapies with poor compliance due to pain and toxicity. He was eventually treated with intrastromal voriconazole and Miltefosine without improvement and eventually had PACK-CXL with resolution of his infection and pain. CONCLUSION: PACK-CXL was associated with a dramatic improvement in a case of recalcitrant Acanthamoeba keratitis unresponsive to both traditional and novel therapies and may be a viable alternative or adjunctive therapy for Acanthamoeba keratitis.

Combined Photoactivated Chromophore for Infectious Keratitis-Corneal Collagen Cross-Linking (PACK-CXL) and Therapeutic Penetrating Keratoplasty for Resistant Bacterial Keratitis.

PURPOSE: To report the results of treating resistant bacterial keratitis by corneal collagen cross-linking followed by therapeutic penetrating keratoplasty and to compare with those of therapeutic penetrating keratoplasty alone. METHODS: Retrospective analysis of the medical records of 33 eyes of 33 patients diagnosed with resistant bacterial keratitis. Fourteen eyes (14 patients) were treated with photoactivated chromophore for infectious keratitis corneal collagen cross-linking (PACK-CXL) followed by therapeutic penetrating keratoplasty (TPK) (group I) and 19 eyes (19 patients) were treated by TPK alone (group II). The main outcome measures were graft clarity and the mean best corrected visual acuity at 1, 3, 6, 12 and 18 months after penetrating keratoplasty. RESULTS: The mean age of the patients was 53.6 ± 1.9 years and 52.3 ± 1.8 years in group I and group II, respectively (p = 0.374), the mean ulcer size was 49.9 ± 16.2 mm2 and 54.7.1 ± 15.1 mm2 in group I and group II, respectively (p = 0.239), the mean corneal infiltrate size was 58.2 ± 17mm2 and 59.9 ± 15.7 mm2 in group I and group II, respectively (p = 0.384). Hypopyon was seen in 6 eyes (41.7%) in group I and in 8 eyes (42.1%) in group II. At the last follow-up visit, 12 corneal grafts (85.7%) maintained their clarity in group I while 13 corneal grafts (68.4%) maintained their clarity in group II (p = 0.037) and the mean best corrected visual acuity was 0.84 ± 0.63 log MAR in group I and 1.27 ± 0.81 log MAR in group II (p = 0.024). Postoperatively, one eye (7%) showed graft reinfection in group I that was controlled medically while 5 eyes (26.3%) showed resistant graft reinfection and ended in graft opacification in group II (p = 0.042). CONCLUSION: In resistant bacterial keratitis, priming infected corneas with PACK-CXL before performing TPK improve the results in such cases.

PACK-CXL vs. antimicrobial therapy for bacterial, fungal, and mixed infectious keratitis: a prospective randomized phase 3 trial.

BACKGROUND: Infectious keratitis is a major cause of global blindness. We tested whether standalone photoactivated chromophore corneal cross-linking (PACK-CXL) may be an effective first-line treatment in early to moderate infectious keratitis, compared with standard antimicrobial treatment. METHODS: This is a randomized, controlled, multinational phase 3 clinical trial. Participants in five centers in Egypt, India, Iran, Israel, and China, aged ≥ 18 years, with infectious keratitis of presumed bacterial, fungal, or mixed origin, were randomly assigned (1:1) to PACK-CXL, or antimicrobial therapy. Outcomes measures included healing, defined as time to re-epithelialization of the corneal epithelial defect in the absence of inflammatory activity in the anterior chamber and clearance of stromal infiltrates. Treatment success was defined as the complete resolution of signs of infection. RESULTS: Between July 21, 2016, and March 4, 2020, participants were randomly assigned to receive PACK-CXL (n = 18) or antimicrobial therapy per American Academy of Ophthalmology (AAO) guidelines (n = 21). No participants were lost to follow-up. Four eyes were excluded from the epithelialization time analysis due to treatment failure: two in the antimicrobial therapy group, and two in the PACK-CXL group. Success rates were 88.9% (16/18 patients) in the PACK-CXL group and 90.5% (19/21 patients) in the medication group. There was no significant difference in time to complete corneal re-epithelialization (P = 0.828) between both treatment groups. CONCLUSIONS: PACK-CXL may be an alternative to antimicrobial drugs for first-line and standalone treatment of early to moderate infectious keratitis of bacterial or fungal origin. Trial registration This trial is registered at ClinicalTrials.gov, trial registration number: NCT02717871.

Review of the literature on the currently available evidence for the management of infectious keratitis with PACK-CXL.

Infectious keratitis (IK) is one of the most common causes of monocular blindness worldwide, especially in developing countries and may account for 5.1%-32.3% of all indications for penetrating keratoplasty (PK). However, performing a therapeutic PK on a "hot eye" is associated with a higher incidence of IK recurrence and graft rejection. Standard treatment includes antimicrobials (ATM) and, once the causative pathogen has been identified, must be continued with targeted treatment, depending on antibiogram sensitivity. However, appearance of multiresistant strains to ATM is progressively increasing at an alarming rate. Besides that, the diversity of the causative microorganisms (bacteria, fungi, parasites, viruses) may hinder the clinical diagnosis and secondarily the proper treatment from the beginning. It is estimated that only 50% of eyes will have a good visual result if the correct therapy is delayed. All these factors make the identification of alternatives to ATM treatment of paramount importance. Due to the ATM properties of photoactivated chromophore (riboflavin, RB) and ultraviolet (UV) light of wavelength (λ) 200-400 nanometers (nm), used in multiple medical and non-medical applications for disinfection, photoactivated chromophore for corneal cross-linking (CXL) of IK (PACK-CXL), as an addition to the therapeutic arsenal for the management of IK has been proposed. It must be differentiated from CXL used for the management of progressive keratoconus (KC). The objective of this review is to update the available evidence on the efficacy and safety of PACK-CXL in IKs.

Photoactivated Chromophore Corneal Collagen Cross-Linking for Infectious Keratitis (PACK-CXL)-A Comprehensive Review of Diagnostic and Prognostic Factors Involved in Therapeutic Indications and Contraindications.

Infectious keratitis is a severe infection of the eye, which requires urgent care in order to prevent permanent complications. Typical cases are usually diagnosed clinically, whereas severe cases also require additional tools, such as direct microscopy, corneal cultures, molecular techniques, or ophthalmic imaging. The initial treatment is empirical, based on the suspected etiology, and is later adjusted as needed. It ranges from topical administration of active substances to oral drugs, or to complex surgeries in advanced situations. A novel alternative is represented by Photoactivated Chromophore Corneal Collagen Cross-Linking (PACK-CXL), which is widely known as a minimally invasive therapy for corneal degenerations. The purpose of this review is to identify the main diagnostic and prognostic factors which further outline the indications and contraindications of PACK-CXL in infectious keratitis. Given the predominantly positive outcomes in the medical literature, we ponder whether this is a promising treatment modality, which should be further evaluated in a systematic, evidence-based manner in order to develop a clear treatment protocol for successful future results, especially in carefully selected cases.

Photoactivated Chromophore for Keratitis-Corneal Collagen Cross-Linking (PACK-CXL) Improves Outcomes of Treatment-Resistant Infectious Keratitis.

PURPOSE: To investigate the efficacy of photoactivated chromophore corneal collagen cross-linking (PACK)-CXL in the management of treatment-resistant infectious keratitis. DESIGN: Observational cohort study. PARTICIPANTS: Forty-two eyes from 41 patients with treatment-resistant infectious keratitis. METHODS: Eyes underwent PACK-CXL treatment with the Dresden modified protocol in addition to standard antimicrobial therapy. The primary endpoint was the size of the corneal ulcer. Descriptive statistics, Wilcoxon rank test, McNemar test and Spearman correlation coefficient were used for statistical analysis, and p values lower than 0.05 were considered statistically significant. RESULTS: Success rate at third postoperative month was of 90.5%. Statistical analyses showed a significant effect of (PACK)­CXL with standard antimicrobial therapy to reduce corneal ulcer size (p=0.031). CONCLUSION: As adjuvant therapy to standard antimicrobial treatment, PACK-CXL improves the outcomes in patients with treatment-resistant corneal ulcers.

Management of infectious keratitis following uneventful small-incision lenticule extraction using a multimodal approach - A case report.

A 42-year-old female presented with pain, photophobia, and superficial corneal infiltrates in mid-periphery in the left eye, after 2 days of uneventful bilateral SMILE procedure. Inspite of the medical treatment with fortified antibiotics, the infection spread to the interface, close to visual axis reducing UDVA from 20/16 to 20/80. Immediate surgical intervention in the form of scraping of interface lesions with 26G needle, interface wash with antibiotics and photoactivated chromophore for keratitis (PACK-CXL) was performed. After 24 h of bacterial culture Staphylococcus aureus was yielded. Interface wash and PACK-CXL was repeated after 48 h by which infiltrates reduced and early scarring was observed by 10th post-op day. Subsequent topical steroids helped in limiting scar formation and UDVA improved to 20/30 at the final visit. Combined approach of interface wash with antibiotics and PACK-CXL may be a safe and effective modality in treating early onset infectious keratitis following SMILE surgery.