Severe reactive ischemic posterior segment inflammation in acanthamoeba keratitis: a new potentially blinding syndrome.

OBJECTIVE: To describe a newly recognized clinical syndrome in Acanthamoeba keratitis consisting of severe reactive ischemic posterior segment vascular inflammation. DESIGN: Noncomparative, retrospective, single-institution observational case series. PARTICIPANTS: Five eyes of 5 patients with Acanthamoeba keratitis. METHODS: A retrospective review of the records of patients diagnosed with Acanthamoeba keratitis between January 1, 1995, and December 1, 2005, was conducted to identify those who underwent eventual enucleation. Five enucleated eyes of 118 eyes with Acanthamoeba keratitis were identified. MAIN OUTCOME MEASURES: History, clinical examination results, available laboratory study results, and histopathologic examination results. RESULTS: Histopathologic examination showed Acanthamoeba cysts in the cornea in 4 eyes, whereas it failed to demonstrate amebic cysts or trophozoites in the posterior segment of all eyes studied and unexpectedly revealed chronic chorioretinal inflammation with perivascular lymphocytic infiltration and diffuse neuroretinal ischemia in 4 of 5 eyes. Retinal artery thrombosis was present in 3 of the 4 involved eyes, and central retinal artery and vein thrombosis was found in 1 eye. Hematologic studies in 3 patients showed abnormal anticardiolipin antibody levels in 1 patient and factor V Leiden deficiency in another. CONCLUSIONS: Prolonged Acanthamoeba keratitis can result in a severe sterile ischemic posterior segment inflammation that is potentially blinding, especially in patients with underlying hypercoagulation disorders.

Tandem scanning confocal corneal microscopy in the diagnosis of suspected acanthamoeba keratitis.

OBJECTIVE: To evaluate the role of in vivo corneal tandem scanning confocal microscopy (TSCM) in the definitive diagnosis of suspected Acanthamoeba keratitis (AK). DESIGN: Noncomparative interventional single-institution case series. METHOD: A retrospective case review of patients consecutively referred with suspected AK and undergoing corneal TSCM was performed. RESULTS: A total of 63 cases that met the inclusion criteria for the study were referred for diagnostic evaluation. Tandem scanning confocal microscopy demonstrated Acanthamoeba cysts/trophozoites in 54 cases and fungal hyphae in 2, whereas 1 case was positive for both Acanthamoeba and fungus. Culture of the cornea or contact lenses was carried out in 35 cases, 9 of which were positive for Acanthamoeba. Six of the TSCM-positive cases also underwent corneal biopsy, being positive for Acanthamoeba in only 2. Six patients were negative for Acanthamoeba on TSCM, the etiology being fungal in 1 case, as shown by subsequent culture. One patient was positive on culture for Acanthamoeba but falsely negative by TSCM, which was limited by poor cooperation during the examination. Two cases initially masqueraded as Acanthamoeba keratitis but showed fungus on TSCM. Mean follow-up was 14 months. CONCLUSION: In vivo corneal TSCM can establish the diagnosis of Acanthamoeba keratitis rapidly and noninvasively, particularly when conventional microbiology is inconclusive.

Ocular surface restoration using non-surgical transplantation of tissue-cultured human amniotic epithelial cells.

PURPOSE: To assess the effect of tissue-cultured human amniotic epithelial cells (AECs) in restoring the ocular surface, transplanted using a collagen shield seeded with AECs supported by a soft contact lens. DESIGN: Prospective interventional single-institutional case series with crossover controls. METHODS: Three eyes in three patients were identified with persistent corneal epithelial defects (PEDs) refractory to medical therapy. Two cases were secondary to neurotrophic keratopathy, while one case was attributable to longstanding alkali injury. AECs were isolated from serologically screened donor human placenta, seeded onto collagen corneal shields, and incubated in tissue culture medium for 7 days. These collagen shields were placed over the PED and supported by an overlying soft contact lens. The collagen shields dissolved by 72 hours, and the contact lenses were removed after this time. This cycle was repeated every week until healing was achieved. As a crossover control, collagen shields without AECs were placed in the same eye 1 week before placing collagen shields containing AECs. The PED was assessed by vital staining and slit-lamp color photography. RESULTS: The PEDs had a mean duration of 4 months and involved 20% to 37% of the corneal surface area, one case secondary to longstanding alkali injury and two cases attributable to neurotrophic keratopathy. No change in PED size was observed in those control eyes receiving collagen shields without AECs. Complete resolution of the PED was seen after two cycles of AEC-seeded collagen shield in one case, and four cycles in two cases, from 7 to 12 weeks following treatment in all patients. No loss of visual acuity was seen and clinical improvement was maintained in all cases, with a mean follow-up of 6.3 months. CONCLUSIONS: Nonsurgical transplantation of tissue-cultured AECs on a collagen shield provides a promising approach to restoring the ocular surface in cases of PED.

Confocal assessment of the corneal response to intracorneal lens insertion and laser in situ keratomileusis with flap creation using IntraLase.

PURPOSE: To assess the response of the cornea to hydrogel intracorneal lens (ICL) insertion or laser in situ keratomileusis (LASIK) with IntraLase (IntraLase Corp.) at the cellular level. SETTING: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. METHODS: Twenty patients (29 eyes) were evaluated by in vivo confocal microscopy 1 to 6 months postoperatively: 20 eyes had LASIK with flap creation by IntraLase, and 9 eyes had ICL insertion (8 following IntraLase). RESULTS: For LASIK with IntraLase, keratocyte activation and/or interface haze was detected in 8 of 20 eyes. The remaining eyes had interface particles but no cell activation. Keratocyte activation was generally limited to a few cell layers adjacent to the interface. However, 2 patients exhibited multiple layers of activation and increased extracellular matrix (ECM) reflectivity (haze) surrounding the interface by confocal microscopy. Both patients also had clinical haze and photophobia. For ICLs, following insertion, 5 of 9 eyes had activated keratocytes adjacent to the implant surfaces. The largest amount of cell activation and ECM haze detected by confocal microscopy was in 2 patients with significant clinical haze. Structures with an epithelioid morphology were detected on some implant surfaces. Epithelial thickness was 33.3 microm +/- 2.3 (SD) in the ICL eyes and 49.2 +/- 6.5 microm in the LASIK with IntraLase eyes. CONCLUSIONS: Both LASIK with IntraLase and ICL insertion following IntraLase induced keratocyte activation, which may underlie clinical observations of haze in some patients. Intracorneal lens implant also induced thinning of the overlying corneal epithelium.

Results of penetrating keratoplasty for visual rehabilitation after Acanthamoeba keratitis.

PURPOSE: To assess the results of penetrating keratoplasty in quiet eyes after resolution of Acanthamoeba keratitis. DESIGN: A retrospective interventional case series. METHODS: Penetrating keratoplasty was undertaken in 13 eyes of 13 patients with an average age of 29 +/- 13 years and a history of Acanthamoeba keratitis that was diagnosed by culture and/or confocal microscopy between January 1995 and September 2004. All eyes were observed for at least 3 months (average, 5 months) after the discontinuation of antiamebic therapy that had been administered for at least 4.5 months. In vivo confocal microscopy was used to ensure that no residual amoeba were present before the operation. Two keratoplasties were combined with a valve insertion; five keratoplasties were combined with cataract extraction, and one keratoplasty was preceded by a ciliary laser ablation. RESULTS: Postoperative best-corrected visual acuity ranged from 20/40 to 20/15, with the exception of one eye with advanced glaucoma that did not improve from a preoperative vision of light perception. No eye experienced rejection or amoebic recurrences, and 12 grafts remained clear throughout the follow-up period (8 months to 9 years; median, 23 months). One graft failed at 4 months because of uncontrolled glaucoma. The eye was regrafted, and the graft remained clear during the 28 months of follow-up evaluation. Two eyes with preoperatively diagnosed glaucoma needed subsequent surgery to control their intraocular pressure. CONCLUSION: Penetrating keratoplasty for visual restoration after Acanthamoeba keratitis appears to have an excellent long-term prognosis, provided amoebic infection has resolved and concurrent glaucoma is controlled.

Intraocular Lens Opacification following Intracameral Injection of Recombinant Tissue Plasminogen Activator to Treat Inflammatory Membranes after Cataract Surgery.

Purpose. To report 7 cases of intraocular lens (IOL) opacification following treatment of postoperative anterior chamber fibrin with recombinant tissue plasminogen activator (rtPA) after cataract surgery. Methods. Retrospective case series of 7 eyes in 7 patients who developed IOL opacification after receiving rtPA for anterior chamber inflammatory membrane formation resulting from phacoemulsification cataract surgery. Three explanted IOLs were investigated with light microscopy, histochemical analysis, scanning electron microscopy, and X-ray spectrometry. Results. All patients underwent uncomplicated cataract surgery and posterior chamber hydrophilic IOL implantation. Anterior chamber inflammatory membranes developed between 1 and 4 weeks of surgery and were treated with intracameral rtPA. IOL opacification was noted between 4 weeks and 6 years after rtPA treatment with reduced visual acuity, and IOL exchange was carried out in 3 patients. Light microscopy evaluation revealed diffuse fine granular deposits on the anterior surface/subsurface of IOL optic that stained positive for calcium salts. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS) confirmed the presence of calcium and phosphate on the IOL. Conclusions. Intracameral rtPA, though rapidly effective in the treatment of anterior chamber inflammatory membranes following cataract surgery, may be associated with IOL opacification.

Keratoconus and granular dystrophy.

Concurrent bilateral keratoconus and granular dystrophy is reported in a 32-year-old patient with decreased vision. Initially contact lenses were attempted unsuccessfully to treat the conditions. There are a handful of other reports of these combined pathologies in the literature, and the likelihood of a chance cause or possible genetic linkage between the conditions is discussed.

Study of fluid ingress through clear corneal incisions following phacoemulsification with or without the use of a hydrogel ocular bandage: a prospective comparative randomised study.

PURPOSE: To assess the use of a hydrogel ocular bandage (HOB) on clear corneal incisions in phacoemulsification cataract surgery and determine whether HOB reduces ocular surface contaminants ingress after routine surgery. METHODS: In this prospective randomized controlled study, thirty eyes of patients undergoing uneventful phacoemulsification were recruited consecutively and randomly assigned to have a HOB applied to the corneal incision at the end of the surgery or not. At the end of the surgery, trypan blue (TRB) was instilled on the ocular surface, aqueous fluid was aspirated from the anterior chamber (AC) and its optical density was measured using ultraviolet spectrophotometry. The corneal incisions were examined postoperatively using anterior segment optical coherence tomography. Main outcome measures were concentration of TRB in the AC, corneal incision architecture, intraocular pressure (IOP) and Seidel test. RESULTS: All incisions were Seidel negative. The mean IOP in the immediate postoperative period was 18.1 ± 5.48 mmHg for the intervention group and 16.9 ± 5.7 mmHg for the control group (p > 0.05). No architectural differences of the incisions between the two groups were noted. The total mean length of the three-step corneal incisions in the two groups was 2261.2 ± 96.92 µm and 2263 ± 119.75 µm, respectively (p > 0.05). No trace of TRB was detected in any of the samples. CONCLUSION: Proper surgical wound construction without the use of a HOB is efficient in preventing the ingress of fluid through the main corneal incision postoperatively.

Management of patients with herpes simplex virus eye disease having cataract surgery in the United Kingdom.

To standardize the management of patients with herpetic eye disease scheduled for cataract surgery, a questionnaire was sent to each fellow of the Royal College of Ophthalmologists registered as a consultant with a subspecialty interest in cornea. Most respondents agreed that disease stability was required before cataract surgery was offered; 62.3% would operate on patients in whom the disease had been quiescent for 3 to 6 months. The decision to prescribe prophylactic antivirals divided the respondents, with 58.8% in favor of starting antiviral treatment. Most respondents (72.46%) did not start topical antiviral treatment. In regard to changing topical steroid use postoperatively, 80.9% would not change their routine regimen. Oral acyclovir was the first line of treatment for 92.5%. The conclusions were that a significant period of inactivity should be considered before cataract surgery is performed in patients with herpes simplex virus eye disease. Oral antiviral prophylaxis is common clinical practice, but no change in routine postoperative steroid use is needed.

Cyclofenil as a possible cause of non-arteritic anterior ischaemic optic neuropathy.

A 27-year-old woman receiving the steroid drug cyclofenil as a fertility adjunct, experienced blurred vision 24 h after missing a dose and taking a double dose to 'catch up' with her therapeutic protocol. She was found to have a non-arteritic anterior ischaemic optic neuropathy with a visual hemifield defect and impaired optic nerve function, which has not since shown any recovery. This case highlights the prothrombotic potential for the drug when used above normal dosing range, and is therefore of great guidance for those initiating it as a fertility treatment, or in unlicensed use.

Advances in the diagnosis and treatment of acanthamoeba keratitis.

This paper aims to review the recent literature describing Acanthamoeba keratitis and outline current thoughts on pathogenesis, diagnosis, and treatment as well as currently emerging diagnostic and treatment modalities.

Stabilization of bilateral progressive rheumatoid corneal melt with infliximab.

Purpose. To report the use of infliximab in the rapid stabilization of a case of progressive, bilateral rheumatoid peripheral ulcerative keratitis (PUK) that failed to respond to conventional immunosuppressive therapy. Methods. A single interventional case report. Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN) and methotrexate (MTX) were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT), and penetrating keratoplasty (PKP). Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation. Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment.

Keratouveitis as a first presentation of relapsing polychondritis.

This paper provides images and a description of an unusual manifestation of relapsing polychondritis presenting initially with isolated ocular signs, mimicking infective keratitis. We present an interventional case report of a 75-year-old man who presented with marked left ocular irritation and photophobia. Ophthalmological examination disclosed corneal intrastromal infiltrate and hypopyon which failed to respond to intensive antimicrobial drops. He later went on to develop bilateral auricular chondritis. Relapsing polychondritis was diagnosed. Treatment with topical and oral corticosteroids resulted in marked improvement of the corneal infiltrate and resolution of the auricular inflammation. The paper highlights the importance of considering connective tissue inflammatory conditions in any stromal keratitis unresponsive to antimicrobial treatment.

Diagnostic accuracy of microbial keratitis with in vivo scanning laser confocal microscopy.

AIMS: To determine the accuracy of diagnosing microbial keratitis by masked medical and non-medical observers using the Heidelberg Retina Tomograph II/Rostock Cornea Module in vivo confocal microscope. METHODS: Confocal images were selected for 62 eyes with culture- or biopsy-proven infections. The cases comprised 26 Acanthamoeba, 12 fungus, three Microsporidia, two Nocardia and 19 bacterial infections (controls). The reference standard for comparison was a positive tissue diagnosis. These images were assessed on two separate occasions by four observers who were masked to the tissue diagnosis. Diagnostic accuracy indices, kappa statistic and percentage agreement values were calculated. The Spearman correlation coefficient (r(s)) was calculated for the number of correct diagnoses versus duration of disease. RESULTS: The highest sensitivity and specificity values were 55.8% and 84.2%, respectively, and the lowest sensitivity and specificity values were 27.9% and 42.1%, respectively. The highest positive and lowest negative likelihood ratios were 2.94 and 0.59, respectively. Agreement values were: fair to moderate (kappa 0.22-0.44) for reference standard versus observer diagnosis, moderate to good in intraobserver variability (repeatability, kappa 0.56-0.88) and poor to moderate in interobserver variability (reproducibility, kappa 0.15-0.47). The correct diagnosis was associated with duration of disease for Acanthamoeba keratitis (r(s)=0.60, p=0.001). CONCLUSIONS: The diagnostic accuracy of microbial keratitis by confocal microscopy is dependent on observer experience. Intraobserver repeatability was better than interobserver reproducibility. Difficulty in distinguishing host cells from pathogenic organisms limits the value of confocal microscopy as a stand-alone tool in diagnosing microbial keratitis.