Corneal Perforation in a Patient Treated with Atezolizumab-Bevacizumab Combination Therapy for Unresectable Hepatocellular Carcinoma.

BACKGROUND Immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1), or its ligand PD-L1, are the mainstay treatment for several metastatic malignant conditions. ICIs are associated with multiple toxic adverse events affecting various organs, known collectively as immune-related adverse events (irAEs). Dry eye, uveitis, ocular myasthenia, and cicatrizing conjunctivitis are well-recognized ocular irAEs associated with ICIs. CASE REPORT We present a case of 69-year-old man who presented with paracentral, punch-out corneal perforation in the left eye, associated with bilateral severe ocular surface disease 3 weeks after receiving the second dose of atezolizumab-bevacizumab combination therapy for the treatment of unresectable hepatocellular carcinoma. Corneal gluing using cyanoacrylate glue was performed along with bandage contact lens application and temporary tarsorrhaphy to seal the corneal perforation and improve the ocular surface. On the subsequent follow-ups, the corneal glue was unstable and dislodged. Thus, penetrating keratoplasty was performed to salvage the globe along with holding the combination therapy. At the 8-month follow-up, the graft remained clear, and the ocular surface improved substantially in both eyes. CONCLUSIONS Ocular irAEs associated with immune-modulating agents can lead to vision-threatening complications. Therefore, communications between oncologists and ophthalmologists in a multidisciplinary team would be of utmost importance for early detection and timely management of any ocular-related adverse events associated with the use of immunotherapy agents.

Fungal Keratitis and Corneal Perforation as a Rare Complication of Corneal Collagen Cross-Linking Treatment.

PURPOSE: The aim of this study was to report a case of fungal keratitis with subsequent corneal perforation after corneal collagen cross-linking (CXL) treatment performed for keratoconus. CASE REPORT: A 20-year-old woman presented with redness and discharge in the left eye. She had a history of bilateral CXL procedure performed for keratoconus elsewhere 4 days earlier. The visual acuity was hand motion in the left eye. Slit-lamp examination revealed extended corneal melting with surrounding infiltrates. The patient was hospitalized, and corneal epithelial scraping samples were sent for microbiological assessment. In the meantime, empirical antibiotic therapy (fortified topical antibiotics: vancomycin 50 mg/mL, ceftazidime 50 mg/mL, and fluconazole 2 mg/mL q1 hour) was initiated. In direct microscopy of the corneal scraping, septate hyaline fungal hyphae were detected and topical fluconazole was switched to topical voriconazole (10 mg/mL). Three days after hospitalization, corneal melting progressed to perforation and corneal suturing with 10-0 monofilament was performed to reform the anterior chamber. Complete resolution of keratitis with residual scarring was noticed in 2 weeks. Three months later, penetrating keratoplasty was performed to obtain better visual acuity. CONCLUSIONS: CXL with riboflavin has become a common procedure to prevent keratoconus progression by strengthening the biomechanical specialties of the cornea. Although the treatment itself has been used in the management of microbial keratitis and related corneal melting, fungal keratitis and corneal perforation after a CXL procedure for keratoconus might also be detected. Clinicians should be aware of this rare but devastating complication of CXL treatment and start prompt treatment when suspected.

Perforation in interstitial keratitis associated with hidradenitis suppurativa: medical and surgical management.

We present a case of bilateral interstitial keratitis leading to perforation in a woman with hidradenitis suppurativa (HS). A woman in her mid-20s with a history of HS and Grave's disease was referred to the corneal service with loss of vision and pain in both eyes since childhood. She was found to have circumferential thinning and steepening affecting her peripheral cornea bilaterally. Corrected distance visual acuity with spectacles was in the right eye 6/7.5, and in the left 6/30, with local thinnest area of 209 and 217 µm in the right and left eyes, respectively. She experienced recurring episodes of redness and irritation, and perforation occurred. The corneal perforation was managed with cyanoacrylate glueing, followed by a local conjunctival flap. Systemic immunosuppression with mycophenolate mofetil and adalimumab was commenced, with improvement after 18 months of treatment. Dermatologists and ophthalmologists should be aware of this association given its potential severity.

Bilateral Corneal Perforation in a Patient Under Anti-PD1 Therapy.

ABSTRACT: Immune checkpoint inhibition has improved the clinical outcomes for numerous patients with cancer. However, the downside is a whole new spectrum of immune-related adverse events. We report a 68-year-old man with a history of nonsmall cell lung cancer presenting with a spontaneous corneal perforation in the right eye after 22 cycles of pembrolizumab. In addition, a chronic central nonhealing epithelial defect developed after performing a penetrating keratoplasty. Treatment with autologous serum drops resulted in complete healing of the corneal ulcer, where other conventional therapies had no effect. One month after reinitiating pembrolizumab therapy, our patient presented again with a corneal perforation in the fellow eye. This case describes relapsing sterile ulcerations associated with pembrolizumab use and presents an unexpected cure.

Treatment of spontaneous corneal perforation secondary to undiagnosed Sjögren's syndrome using regenerating agent and autologous serum eye drops.

PURPOSE: The aim of this study was to report a case of sterile corneal ulcer leading to perforation, which was treated effectively with autologous serum eye drops, topical regenerative agent (poly-carboxymethylglucose sulfate), steroids, and systemic immunosuppression in a patient with undiagnosed primary Sjögren's syndrome. METHODS: A 74-year-old female presented with a month's history of gradually worsening blurry vision in her left eye. Ophthalmic examination revealed a central descemetocele with excessive corneal stromal melting and absence of signs of infection. A bandage contact lens was applied for tectonic support along with topical corticosteroid and antibiotic drops. Autoimmune screen disclosed a diagnosis of Sjögren's syndrome, and the patient was commenced on systemic immunosuppression. Forty-eight hours after presentation, the patient developed a localized corneal perforation, presenting with a flat anterior chamber. RESULTS: Urgent amniotic membrane transplantation was arranged while topical dexamethasone, moxifloxacin, and autologous serum eye drops were administered. After 24 h of intensive topical treatment, a significant reforming of the anterior chamber and subsequent gradual regeneration of the corneal stroma were noted, thus postponing amniotic grafting. The patient remained under close monitoring, showing progressive clinical improvement. Regenerating agent eye drops (Cacicol20®) were also applied over the next month, with careful and slow tapering of topical dexamethasone. Further improvement of corneal thickness was observed, and visual acuity increased to 20/80. CONCLUSION: This case report demonstrates the successful medical treatment of an autoimmune-related sterile corneal perforation without surgical intervention, highlighting the fact that early diagnosis and rigorous medical treatment with autologous serum and regenerating agent eye drops can effectively aid tissue regeneration and favorable visual rehabilitation.

[Cyanoacrylate adhesive in surgrical treatment of corneal perforation (clinical case)]. / Primenenie tsianoakrilatnogo kleya v khirurgicheskom lechenii perforatsii rogovitsy (klinicheskoe nablyudenie).

In modern ophthalmological practice, three types of adhesives are most often used: synthetic (cyanoacrylate), biological (fibrin), and polyethylene glycol. Cyanoacrylate adhesive is very strong and polymerizes quickly, however, is generally more toxic compared to other types of adhesives, especially if applied to highly vascularized tissues. It is also believed to have bacteriostatic activity and suppress progressive stroma lysis within the area of ulceration by inhibiting polymorphonuclear leukocytes that exhibit collagenolytic and proteolytic activity. The article presents a clinical case of effective use of Russian-made cyanoacrylate (sulfacrylate) adhesive for the treatment of corneal perforation in a patient with neurotrophic keratopathy. The use of polymer glue can be an effective, affordable, and safe alternative to other methods of urgent treatment of corneal perforations and deep ulcers, as shown by this case and literature data. Depending on the lesion location and prognosis for vision, the method can be used either independently or become a treatment stage before keratoplasty. The latter would enable delayed transplantation with lower risk of complications.

Efficacy of cyanoacrylate tissue adhesive in the management of corneal thinning and perforation due to microbial keratitis.

PURPOSE: Report the efficacy of cyanoacrylate tissue adhesive (CTA) application in the management of corneal thinning and perforations associated with microbial keratitis. METHODS: A retrospective review of consecutive patients who underwent CTA application for corneal thinning and perforation secondary to microbiologically proven infectious keratitis between 2001 and 2018 at a single center. We defined successful CTA application as an intact globe without tectonic surgical intervention. RESULTS: The cohort included 67 patients, and 37 presented with corneal perforation while 30 had corneal thinning. The perforation/thinning was central/paracentral in 43 eyes and peripheral in 23 eyes. The underlying infectious etiologies were monomicrobial in 42 cases (35 bacterial, 3 fungal, 2 viral, and 2 acanthamoeba cases) and polymicrobial in 25 cases (22 polybacterial cases and 3 cases with a combination of Gram positive bacteria and fungus). The median duration of glue retention was 29 days. The CTA success rate was 73%, 64%, and 44% at 10, 30, and 180 days, respectively. CTA application appears more successful in monomicrobial (vs. polymicrobial) and Gram positive bacterial (vs. Gram negative) keratitis but the differences are statistically non-significant. The location of perforation/thinning and the use of topical corticosteroid were not associated with CTA failure. CONCLUSION: CTA was moderately effective in restoring globe integrity in severe corneal thinning and perforation secondary to microbial keratitis in the short term. However the majority of patients require tectonic surgical intervention within 6 months. CTA application success is not significantly associated with the location of thinning/perforation or the use of topical corticosteroid.

Cyanoacrylate Tissue Adhesive for the Treatment of Corneal Thinning and Perforations: A Multicenter Study.

PURPOSE: To examine the outcomes of cyanoacrylate tissue adhesive (CTA) application for impending or frank corneal perforations and assess for predictors of treatment response. METHODS: A multicenter cohort study was conducted to assess the clinical outcomes of adult patients who underwent CTA gluing for impending or frank corneal perforations between 2013 and 2018. The primary outcome was the proportion of successful CTA applications, defined as tectonic stability of the globe without subsequent keratoplasty (KP). Secondary outcomes included visual acuity and success of subsequent surgical interventions, if performed. RESULTS: Fifty-three eyes of 52 patients were included in this study [56% women; mean age at presentation 70 ± 13 years; median length of follow-up of 387 days (interquartile range: 191-704)]. Medical comorbidities were present in 62% of patients. The most common etiologies for perforations included infections (43%) and Sjogren disease (9%). Of the CTA-treated eyes, 22% had a complete resolution of the corneal lesion. Fifty-four percent of patients underwent KP. Longer duration of CTA treatment was associated with CTA success (P = 0.04). For patients requiring KP, 71% were successful and 29% failed. There is no significant difference in the median time delay between patients with successful and failed KPs (P = 0.4). CONCLUSIONS: CTA may be considered a stand-alone treatment for corneal perforations. It yielded a success rate of 22%. Failed CTA treatment occurred quickly, largely because of the severity of presentation. In cases requiring KP, the delay between glue application and surgery did not influence the PK success.

Corneal melt secondary to eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody-associated vasculitis that can affect any organ system. It is most often characterised by chronic airway inflammation along with prominent peripheral blood eosinophilia, although the disease can affect the cardiovascular, gastrointestinal, renal or central nervous systems. Ocular manifestations are uncommon and when they do occur, are varied in their clinical presentations. To the best of our knowledge, this is the first case of corneal melt secondary to EGPA to have been reported.

Outcomes of Cyanoacrylate Tissue Adhesive Application in Corneal Thinning and Perforation.

PURPOSE: To report the outcomes of cyanoacrylate tissue adhesive (CTA) application in corneal thinning and perforation. METHODS: A retrospective interventional case series of 137 patients receiving CTA for corneal thinning and perforation in 140 eyes between 2001 and 2018 at a single center was reviewed. Success rate and factors associated with glue failure were analyzed. RESULTS: Median age of the cohort was 63 years and 69 (50%) were women. One hundred fifteen patients (84%) had at least 1 systemic condition, 46 (34%) had autoimmune diseases. Eighty-nine eyes (64%) presented with perforation and 51 (36%) with thinning. The perforation/thinning was central/paracentral in 82 eyes (59%) and peripheral in 57 eyes (41%). Median size of perforation was 3.1 mm. Causes of perforation and thinning were microbial infection in 75 (55%), sterile melt in 49 (35%), laceration in 10, and keratoprosthesis melt in 8 eyes. Median glue retention was 58 days. Success rate of glue application (defined as intact globe without surgical intervention) was 72%, 61%, and 46% at 10, 30, and 90 days after glue application, respectively. Larger size of perforation/thinning, perforation (vs. thinning), and single glue application (vs. multiple) were correlated with higher failure rate. Systemic conditions, use of topical corticosteroid, etiologies, and location of perforation/thinning were not significantly correlated with glue failure. CONCLUSIONS: CTA application was moderately effective in stabilizing corneal perforation and thinning in the very short-term. Multiple applications are often required. Maintenance of globe integrity after glue application decreases with time and the need for surgical intervention remains high.

Hydration of small leaking corneal perforations with cefuroxime.

PURPOSE: To describe a new technique for sealing small corneal perforations after penetrating trauma. METHODS: Corneal perforations in six eyes were sealed using a stromal cefuroxime hydration technique. This technique is identical to the current method used to seal leaking incisions upon completion of cataract surgery except for the use of cefuroxime instead of balanced salt solution. Additionally, cefuroxime was intentionally injected into the anterior chamber. A therapeutic contact lens was used after the hydration. Comparison was made in eight eyes with small traumatic corneal perforation that was sealed using therapeutic contact lenses without hydration. RESULTS: This novel technique was applied in six cases, with leakage stopping immediately following hydration in each of these eyes. In cases presenting with a shallow or flat anterior chamber, this maneuver produced immediate reformation of the chamber. Of note, the corneal scars after hydration were minimal with little effect on visual acuity. When compared to eyes with small corneal perforations which were sealed with therapeutic contact lenses without hydration, all cases that were hydrated with cefuroxime were sealed immediately, as opposed to cases treated without hydration. Furthermore, the eyes that underwent hydration with cefuroxime had a worse average visual acuity on admission, a better average visual acuity 1 month post-trauma, and a shorter average length of hospitalization. CONCLUSIONS: This new technique offers five major advantages: (1) Immediate sealing of the corneal perforation is achieved. (2) Definitive treatment can be achieved at the slit lamp. (3) Since neither stitches nor glue is applied, healing is achieved with minimal scarring and discomfort. (4) Little equipment is required. (5) Injection of cefuroxime into the anterior chamber provides prophylaxis against infection.

A Case of Late Spontaneous Post-Radial Keratotomy Corneal Perforation Managed With Specialty Lenses.

PURPOSE: To describe a case of spontaneous wound dehiscence 29 years after radial keratotomy (RK) and to illustrate how specialty contact lenses were used for tectonic support and optic correction. SETTING: Tertiary referral center for corneal pathology. DESIGN: Case report. RESULTS: In November 2014, a 62-year-old woman presented to the emergency department with a spontaneous corneal perforation in her left eye. Her ocular history was significant only for uncomplicated RK surgery performed in 1985 to correct myopia (-5.50 D) in both eyes. At the slit-lamp pronounced, bullous edema was seen in the inferotemporal quadrant of the left cornea with internal opening of the 3.30- and 5-o'clock positions incisions and severe localized thinning and aqueous leakage at the 5-o'clock position incision. There was no history of trauma. A conservative approach was adopted: application of a standard bandage lens was effective in tamponading the leakage, allowing the anterior chamber to reform; a custom-made soft lens was worn for tectonic support over a period of 4 months. Finally, visual acuity was restored to 20/20-by fitting a scleral lens. CONCLUSION: Spontaneous corneal perforation is a rare but more dramatic long-term complication after RK. The pivotal role of appropriately fitted soft bandage lenses in the conservative management of this type of complex perforation is highlighted. For optical correction, a scleral lens was fitted with excellent visual result, illustrating the added value of specialty contact lenses as an alternative to surgery in the management of postrefractive corneas.

[Staged complex treatment of paralytic lagophthalmos (case report)]. / Kompleksnoe poetapnoe lechenie paraliticheskogo lagoftal'ma (klinicheskii sluchai).

Paralytic lagophthalmos, resulting from facial nerve palsy, is a difficult medical and social issue that requires cooperation of different specialists. Complications that arise in paralytic lagophthalmos may cause significant vision loss and even eye loss. Various techniques of paralytic lagophthalmos correction are used to protect the cornea and restore eyelid anatomy and functions. These comprise palliative (conservative), surgical, and alternative treatments (such as botulinum toxin type A therapy). Surgical treatment of paralytic lagophthalmos patients often has to be staged and complex. This article presents a clinical case of a female patient with paralytic lagophthalmos complicated by corneal perforation. Her staged complex treatment included lower eyelid surgery, chemodenervation of the upper eyelid levator and optical reconstructive surgery. The following positive results were achieved: the protective function of the eyelids was restored, residual visual functions - preserved, the risk of eye loss - eliminated, and the asymmetry between the two halves of the face - corrected.

Non-traumatic corneal perforations: aetiology, treatment and outcomes.

PURPOSE: To report aetiology, characteristics, treatment and main outcomes of non-traumatic corneal perforations in a single referral centre. METHODS: A retrospective review of clinical records of patients diagnosed with non-traumatic corneal perforation. The analysed data included demographic characteristics, medical history, initial and final corrected distance visual acuity (CDVA), perforation aetiology, size, location, initial therapy, surgical treatment, ocular integrity and complications. A comparison between non-infectious and infectious groups was performed. Different variables were analysed through a multiple logistic regression analysis for the probability to have at least one more procedure. RESULTS: We included 127 eyes of 116 patients with a mean age of 50 years and a mean follow-up of 11 months. The initial CDVA was 3.00 logarithm of the minimum angle of resolution (logMAR) and the final CDVA was 2.30 logMAR (p>0.5). Regarding treatment, of the 49 eyes with an initial cyanoacrylate patch, 35 eyes (71.4%) had at least one more procedure performed (p>0.001). In comparison, of the 49 eyes with an initial tectonic penetrating keratoplasty (PK), 33 (67.3%) eyes remained stable while 16 (32.7%) eyes needed one or more interventions (p=0.004). In a multiple logistic regression analysis, an initial cyanoacrylate patch represented a probability of 4.7 times to require a subsequent procedure in comparison with an initial PK. Overall, globe integrity was achieved in 96.1% of the cases. CONCLUSIONS: Corneal perforations represent an important cause of ocular morbidity. The use of a cyanoacrylate patch is useful as an initial therapy in corneal perforations; however, procedures such as PK are often necessary to achieve anatomical success, especially in non-infectious aetiologies.

Fonsecaea pedrosoi as a rare cause of acute conjunctival ulceration.

Conjunctival ulceration accompanied with secretion and pain was observed in a 30-year-old male, 3 days after a perforating corneal trauma. Cultures of conjunctival ulcer samples grew Fonsecaea pedrosoi, a major causative agent of chromoblastomycosis that is typically transmitted during trauma. The conjunctival ulcer was successfully treated with amphotericin B, itraconazole, and fluconazole. This case report summarizes the diagnosis and treatment of a conjunctival ulcer due to F. pedrosoi, which is a rare complication of contaminated ocular trauma. To the best of our knowledge, this is the first reported case of F. pedrosoi causing acute conjunctival ulceration in the literature.

Fonsecaea pedrosoi as a rare cause of acute conjunctival ulceration / Fonsecaea pedrosoi como agente raramente associado à úlcera conjuntival aguda

ABSTRACT Conjunctival ulceration accompanied with secretion and pain was observed in a 30-year-old male, 3 days after a perforating corneal trauma. Cultures of conjunctival ulcer samples grew Fonsecaea pedrosoi, a major causative agent of chromoblastomycosis that is typically transmitted during trauma. The conjunctival ulcer was successfully treated with amphotericin B, itraconazole, and fluconazole. This case report summarizes the diagnosis and treatment of a conjunctival ulcer due to F. pedrosoi, which is a rare complication of contaminated ocular trauma. To the best of our knowledge, this is the first reported case of F. pedrosoi causing acute conjunctival ulceration in the literature.

RESUMO O quadro clínico de uma úlcera conjuntival acompanhada de secreção e dor foi observado em homem de 30 anos de idade, 3 dias após um trauma perfurante da córnea. As culturas de uma amostra retirada da úlcera conjuntival foi positiva para Fonsecaea pedrosoi, uma cromoblastomicose, geralmente transmitido após traumatismos. O caso foi tratado com sucesso com a anfotericina B, itraconazol e fluconazol. Este relato de caso reporta o diagnóstico e tratamento de uma úlcera conjuntival causada por F. pedrosoi, que raramente é visto nos olhos expostos a traumatismos contaminados. Até onde sabemos, este é o primeiro caso relatado na literatura de F. pedrosoi causando úlcera conjuntival aguda.