Charles S. Bouchard

Background, Immunology, and Pharmacology

Systemic cyclosporin A (CsA) is currently being used for immunosuppression in solid organ transplantation. Its unique mechanism of action and low myelotoxicity have vastly improved the prognosis for patient survival. A reversible and irreversible nephrotoxicity has complicated its use. CsA works via the inhibition of both lymphokine release and subsequent activation of cytotoxic T cells. The corneal allograft model presents several unique features that make it amenable to local immunosuppressant therapy. Following topical application, CsA corneal levels have been obtained above the experimentally determined levels necessary for local immunosuppression. CsA represents one of a new class of specific, potent immunomodulators, which may improve the prognosis for patients at high risk for allograft rejection.

Extended-wear silicone hydrogel soft contact lenses in the management of moderate to severe dry eye signs and symptoms secondary to graft-versus-host disease.

Purpose. To determine the safety and efficacy of the Focus NIGHT & DAY (CIBA Vision, Duluth, GA) silicone hydrogel contact lens in the management of refractory, moderate to severe dry eye signs and symptoms secondary to graft-versus-host disease (GVHD). Methods. Seven patients with GVHD and moderate to severe dry eye disease as determined by the Ocular Surface Disease Index (OSDI) questionnaire were fitted with a near plano Focus NIGHT & DAY soft contact lens (SCL) used on a 7-night continuous-wear basis. Visual acuity, objective measures of dry eye disease (i.e., Schirmer I, tear breakup time, and corneal fluorescein staining), and OSDI scores were compared before SCL wear and after 1 week and 1 month of SCL wear. Results. There was significant improvement in subjective assessment of dry eye symptoms (initial vs. 1-month OSDI score, 76.8 ± 13.6 vs. 31.2 ± 17.8, P<0.0005, paired t test). In addition, patients had significant improvement in best-corrected visual acuity after 1 month of SCL wear (initial vs. 1-month logMAR visual acuity for the right eye, 0.23 ± 0.050 vs. 0.04 ± 0.027, P<0.007; initial vs. 1-month logMAR visual acuity for the left eye, 0.22 ± 0.049 vs. 0.04 ± 0.020, P<0.007, analysis of variance, Dunnett post hoc). There were no significant changes in results of Schirmer I testing, corneal fluorescein staining, or tear breakup time. No adverse events or complications of SCL wear were observed. Conclusions. The Focus NIGHT & DAY contact lens can improve subjective dry eye symptoms and visual acuity in patients with refractory dry eye disease secondary to GVHD.

Indications and outcomes of amniotic membrane transplantation in the management of acute stevens-johnson syndrome and toxic epidermal necrolysis: a case-control study.

Purpose: To evaluate the indications and outcomes of amniotic membrane transplantation (AMT) performed within the first 2 weeks of presentation in the management of patients with acute Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Methods: A retrospective chart review from January 1998 to May 2011 identified 128 SJS/TEN patients admitted to Loyola University Medical Center Burn intensive care unit. The degree of initial ocular surface inflammation was graded as mild, moderate, or severe within the first 2 weeks of admission. Patients were managed either medically or with amniotic membrane (AM). Outcomes were graded as good [best-corrected visual acuity (BCVA) >20/40], fair (BCVA 20/40 to 20/200 or with ocular surface discomfort, requiring contact lens or reconstructive surgeries), or poor (BCVA <20/200). Results: Of the 182 eyes (91 patients) with documented inpatient eye examinations, 108 eyes (59.4%) had mild or no initial ocular involvement, 37 eyes (20.3%) had moderate, and 37 eyes (20.3%) had severe inflammation. Of the 29 patients (58 eyes) with greater than 1 month of follow-up, 17 patients (33 eyes) were treated with medical management and 13 patients (25 eyes) were treated with early AM. One of the 23 eyes with moderate or severe presentation treated with early AMT (4.3%) resulted in a poor outcome within 3 months compared with 8 of 23 eyes (34.8%) that were medically managed (P = 0.022). Conclusions: We present the first case–control study of the use of AM in the management of acute SJS/TEN. Early use of AMT prevents severe vision loss in SJS/TEN patients with initial moderate or severe ocular surface inflammation.

Retrospective review of graft dislocation rate associated with descemet stripping automated endothelial keratoplasty after primary failed penetrating keratoplasty

Purpose: To report the rate of graft dislocation in patients who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) after a previous penetrating keratoplasty (PKP). Methods: Institutional review board-approved, multicenter, retrospective chart review. Inclusion criteria included: prior failed PKP and subsequent DSAEK. The primary outcomes measured in this study were the presence of a graft dislocation, rate of rebubble, and graft attachment. Additional variables included: presence of a prior glaucoma drainage device, graft-to-host size disparity, number of sutures remaining in PKP, and stripping of the Descemet membrane at the time of DSAEK surgery. Results: Ninety patients (97 eyes) were included in the study. In 31% (30 of 97), the endothelial graft dislocated after surgery. All 30 cases required a rebubble except 1, which reattached spontaneously. Ninety-eight percent (95 of 97) of all grafts remained attached for the duration of the follow-up period. Only 2 eyes (2.2%) required repeat graft. Endothelial grafts dislocated in 67% of patients with glaucoma draining devices. The dislocation rate for grafts larger than the host was 12 of 49 (24%), equal to the host was 3 of 17 (18%), and smaller than the host was 8 of 19 (42%). Dislocations occurred in 5 of 21 (24%) of grafts with sutures remaining and 22 of 76 (29%) of those with all sutures out. Five of 12 (42%) cases of grafts performed without stripping the Descemet had dislocations. Conclusions: The graft dislocation rate in DSAEK procedures after PKP is comparable to that after primary DSAEK cases. Donor grafts that are smaller than the host PKP and the presence of prior glaucoma drainage devices are risk factors for higher rates of graft dislocation.

Effect of topical anti-inflammatory drugs on corneal and limbal wound healing.

Purpose: To examine the effect of topical treatment with either steroidal or nonsteroidal anti‐inflammatory drugs (NSAIDs) on the wound healing of corneal and limbal incisions using histologic criteria. Setting: Loyola University Medical Center, Maywood, Illinois, USA. Methods: Eighteen eyes of 9 cats were used for the study. All right eyes received a temporal limbal incision and the left eyes, a clear corneal incision. All eyes were treated with ofloxacin 0.3% postoperatively for 3 days. The animals were equally divided among 3 groups. Group 1 received topical steroid drops (prednisolone acetate 1%) for 7 days maximum; Group 2 received topical NSAID drops (ketorolac tromethamine 0.5%) for 7 days maximum; Group 3 received no additional treatment. One animal from each group was killed and the eye enucleated 3, 7, or 28 days postoperatively. The eyes were processed for staining with hematoxylin–eosin and smooth muscle actin, and corneal sections were evaluated in a blind fashion by an ophthalmic pathologist. Results: Three and 7 days after surgery (1) the limbal incision exhibited more prominent wound healing than the similarly treated clear corneal incision, and (2) the steroid‐treated corneas had less wound healing than untreated or NSAID‐treated corneas. At 28 days, the wounds in all eyes were almost completely healed. Conclusions: Limbal incisions heal faster than clear corneal incisions. Steroids, but not NSAIDs, inhibit wound healing. Cataract surgery using limbal incisions and postoperative topical NSAIDs may result in faster wound healing and provide a reduced risk of related postoperative complications.

Ocular morbidity associated with airbag deployment: a report of seven cases and a review of the literature.

Purpose. To review ocular injuries secondary to airbag deployment that were seen in our institution and were reported in the literature. Methods. Patients examined at our institution between 1997 and 2000 were evaluated for ocular injuries caused by airbags. A review of the medical literature using Medline was performed. All reports involving ocular injuries secondary to airbags were included in this study. Results. Seven cases from our medical center were identified to involve airbag-related eye injuries. The ages of the patients ranged from 4 to 73 years. Ocular injuries included corneal abrasion, corneal decompensation, corneal alkali injury, hyphema, iris sphincter tears, vitreous hemorrhage, macular retinal pigment epithelium disruption, dislocated posterior chamber intraocular lens, and commotio retinae. A review of the medical literature showed 74 cases involving 80 eyes. The ages of the patients ranged from 2 to 81 years. Males slightly outnumbered females by a ratio of 1.1 to 1.0. The speed of the vehicles ranged from 0 to 65 miles per hour, with an average reported speed of 31 miles per hour. Reported injuries ranged from mild corneal abrasions to open globes. Conclusions. Ocular morbidity secondary to airbag deployment must be recognized as a significant risk for motor vehicle drivers and passengers. Improvements in airbag safety will include increased consumer awareness and manufacturer design modification.

Ocular complications of thermal injury: a 3-year retrospective.

BACKGROUND Diagnosis and treatment of thermal ocular injuries are often delayed because facial burns are usually associated with life-threatening injuries requiring immediate intervention. The purpose of the present study is to review the diagnosis and management of ocular complications associated with thermal burns in a tertiary care burn unit. METHODS In this retrospective study, the charts of patients admitted to the Loyola University Medical Center Burn Unit between January 1993 and January 1996 were reviewed. RESULTS Of the 1,461 patients who were admitted to the burn unit during that period, 155 (10.6%) required ophthalmic consultation. Sixty-one patients (4.2%) had ocular injury, the most common type being periorbital burn and edema followed by corneal involvement. Thirty-one of the 61 patients (51%) received consultation on the day of admission. Six of the 61 patients (10%) required surgical intervention. There was no correlation between number of days to consultation and need for surgical intervention. Patients requiring surgery were more likely to have suffered third-degree burns. CONCLUSION Because it is difficult to predict which patients suffering from thermal burns involving the eyes will require surgical intervention, ophthalmic consultation should be sought early.

Management of ocular conditions in the burn unit: thermal and chemical burns and Stevens-Johnson syndrome/toxic epidermal necrolysis.

Patients in burn intensive care units suffer from potentially life-threatening conditions including thermal or chemical burns and Stevens-Johnson syndrome/toxic epidermal necrolysis. There is often involvement of the ocular surface or adnexal structures which may be present at the time of hospital admission or may develop later in the hospital course. This article will describe the types of ocular burns, the mechanisms and manifestations of Stevens-Johnson syndrome/toxic epidermal necrolysis, the circumstances that may influence outcome, and acute and long-term treatment strategies, including new and evolving options.

Hyperosmolar Stress Induces Neutrophil Extracellular Trap Formation: Implications for Dry Eye Disease

PURPOSE To determine if hyperosmolar stress can stimulate human neutrophils to form neutrophil extracellular traps (NETs) and to investigate potential strategies to reduce formation of NETs (NETosis) in a hyperosmolar environment. METHODS Neutrophils were isolated from peripheral venous blood of healthy subjects and incubated in iso-osmolar (280 mOsM) or hyperosmolar (420 mOsM) media for 4 hours. Neutrophil extracellular traps were quantified using a PicoGreen dye assay to measure extracellular DNA. Two known inhibitors of NETosis, staurosporine and anti-β2 integrin blocking antibody, and two proresolution formyl peptide receptor 2 (FPR2) agonists, annexin/lipocortin-1 mimetic peptide and 15-epi-lipoxin A4, were evaluated as possible strategies to reduce hyperosmolarity-induced NETosis. RESULTS The amount of NETs induced by hyperosmolar medium (420 mOsM) increased linearly over time to 3.2 ± 0.3 times that induced by iso-osmolar medium at 4 hours (P < 0.05). NETosis increased exponentially with increasing osmolarity and was independent of the stimulus used to increase osmolarity. Upon neutrophil exposure to hyperosmolar stress, restoration of iso-osmolar conditions decreased NET formation by 52.7% ± 5% (P < 0.05) but did not completely abrogate it. Among the strategies tested to reduce NETosis in a hyperosmolar environment, annexin-1 peptide was the most efficacious. CONCLUSIONS Hyperosmolarity induces formation of NETs by neutrophils. This NETosis mechanism may explain the presence of excessive NETs on the ocular surface of patients with dry eye disease. Because they reduce hyperosmolarity-induced NETosis, FPR2 agonists may have therapeutic potential in these patients.

The Ophthalmologist's Role in the Management of Acute Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Stevens-Johnson syndrome (SJS) and its more severe variant, toxic epidermal necrolysis (TEN), are relatively rare but have high mortality rates. Survivors are frequently afflicted with severe blinding ocular surface diseases. Recent literature in the areas of ophthalmology and dermatology illustrate that the ophthalmologists role should no longer be considered secondary in the acute management of SJS/TEN. Accurately differentiating SJS or TEN from erythema multiforme majus (EMM) at the onset of the disease is important, because the management approach to these disease entities differs. Systemic cyclosporine and intravenous immunoglobulin have shown some potential as treatments for SJS/TEN, but their efficacies remain controversial. Amniotic membrane transplantation and intravenous corticosteroid pulse therapy at the acute stage have shown promise for preventing late sight-threatening cicatricial complications. An improved staging system for the ocular surface involvement of acute SJS/TEN, as well as better understanding of the underlying destructive pathogenic mechanism, should further improve our ability to predict ocular involvement and develop new therapeutics to abort destructive processes at the acute stage.