Abraham Solomon

The diagnosis and management of dry eye: a twenty-five-year review.

Purpose. To review the advances in the diagnosis, pathogenesis, and management of dry eye disease in the past 25 years. Methods. Literature review. Results. The preocular tear film is a hydrated mucus gel that contains soluble antimicrobial proteins and growth factors that protect and support the ocular surface. The final common pathway in dry eye is a perturbation of the integrated ocular surface/lacrimal gland reflex unit. Diagnostic tests evaluating tear composition and clearance appear to show stronger correlation with the severity of ocular irritation symptoms and keratoconjunctivitis sicca (KCS) than the conventional Schirmer tests. KCS is a condition of abnormal differentiation and mucus production by the ocular surface epithelium that results in a poorly lubricated, abnormally permeable ocular surface that has increased susceptibility to environmental insults. Chronic subclinical ocular surface inflammation appears to play a key role in the pathogenesis of KCS. New therapeutic strategies are aimed at reducing the ocular surface inflammation of dry eye disease. Conclusions. There has been a tremendous increase in knowledge regarding dry eye disease in the past 25 years that has resulted in improved diagnostic classification and new targeted therapies.

Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency☆

PURPOSE To evaluate the long-term outcome of ocular surface reconstruction, including keratolimbal allograft (KLAL) and amniotic membrane transplantation (AMT) with or without penetrating keratoplasty (PKP), in patients with nonambulatory vision secondary to total limbal stem cell deficiency (LSCD). DESIGN Retrospective, non-comparative interventional case series. PARTICIPANTS Thirty-nine eyes in 31 consecutive patients with total LSCD, as defined by impression cytology, who had a preoperative best-corrected visual acuity of less than 20/200 and a minimum follow-up of 12 months. Patients were divided into three groups: group 1 (16 eyes) with chemical burns, group 2 (9 eyes) with Stevens-Johnson syndrome (SJS), and group 3 (14 eyes) with other causes of LSCD, including ocular cicatricial pemphigoid, atopic keratoconjunctivitis, and aniridia. INTERVENTION All patients underwent KLAL and AMT by one surgeon (SCGT). If needed, PKP was performed at the same surgical setting using tissue from the same donor. MAIN OUTCOME MEASURES Cumulative rates of survival of ambulatory vision (> or = 20/200), survival of KLAL, survival of PKP, and incidence of complications. RESULTS Fifty-three KLAL with AMT procedures were performed in 39 eyes, of which 23 eyes received simultaneous PKP at the time of the first KLAL. The mean follow-up was 34.0 +/- 21.5 months (range, 12-117.6). The mean period of ambulatory vision was 23.9 +/- 20.9 months (range, 0-104). The overall survival of ambulatory vision was 53.6% at 3 years and 44.6% at 5 years. The survival of ambulatory vision was significantly worse in SJS compared with other causes (67%, 81%, and 92% for groups 1, 2, and 3, respectively; P = 0.06 for group 1 versus 2, P = 0.0008 for group 1 versus 3). KLAL performed alone resulted in higher survival of ambulatory vision at 2 years (86.1% +/- 9.1%) compared with KLAL with PKP (46.9% +/- 10.6%, P = 0.100). The survival of PKP was significantly worse in SJS compared with the other causes (20.0% +/- 17.9% compared with 55.6% +/- 11.7%, respectively, P = 0.028). After 2 years, the survival of the second KLAL was better than that of the first: 68.2% +/- 15.4% compared with 27.3% +/- 13.4%, respectively (P = 0.041). CONCLUSIONS Ambulatory vision for a period of more than 2 years can be achieved by KLAL with or without PKP in eyes with severe ocular surface disorders caused by total LSCD. However, a progressive decline of the visual outcome and graft survival is evident with time. Performing PKP simultaneously with KLAL may be associated with a less favorable outcome. The failure of KLAL is associated with the loss of donor cells in the recipient. Augmentation of ocular surface defense is essential in securing the success of KLAL and PKP. Future modifications of the surgical procedure and of the immune suppressive protocols may improve survival of the allogeneic grafts and the final visual outcome.

Amniotic membrane transplantation after extensive removal of primary and recurrent pterygia

OBJECTIVE To evaluate the postoperative outcome and the recurrence rate after extensive removal of primary and recurrent pterygia combined with amniotic membrane transplantation. DESIGN A noncomparative interventional case series. PARTICIPANTS Fifty-four eyes in 54 subjects with either primary (n = 33) or recurrent (n = 21) pterygia operated on by one surgeon (SCGT). INTERVENTION All subjects were operated on for pterygia with an extensive excision of the lesion followed by amniotic membrane transplantation and intraoperative injection of a depot corticosteroid. MAIN OUTCOME MEASURES Cumulative rates of conjunctival (grade 3) and corneal (grade 4) recurrence and incidence of complications. RESULTS The mean follow-up was 12.8 +/- 4.3 months for primary and 14.3 +/- 4.9 months for recurrent pterygia. The true recurrence rate (grade 4) was 3.0%, 9.5%, and 5.6% for primary, recurrent, and all pterygia, respectively. The cumulative proportion of recurrence-free eyes at 12 months was 0.90 +/- 0.06 for primary and 0.69 +/- 0.11 for recurrent pterygia (P = 0.047, log-rank test). Removal of the semilunar fold was associated with longer survival times (P = 0.063) and decreased failure rate (P = 0.046). A similar success rate was achieved in double-head pterygia (1 recurrence in 11 eyes). CONCLUSIONS Amniotic membrane transplantation is an effective and safe procedure for pterygium surgery, with a relatively low recurrence rate for both primary and recurrent pterygia. It can be a useful alternative to conjunctival autograft when a large conjunctival defect has to be covered, such as in primary double-head pterygia and in large recurrent pterygia.

Nerve growth factor is preformed in and activates human peripheral blood eosinophils

BACKGROUND Recent studies have shown that nerve growth factor (NGF) is produced by and can act on several immune-inflammatory cells. OBJECTIVES The objective of this study was to study the effects of NGF on human peripheral blood eosinophils and assess whether these cells produce and store NGF. METHODS Eosinophils were purified by negative immunoselection (magnetic cell sorting systems, purity 98% to 100%) from 13 subjects (9 to 26 years old) with mild blood eosinophilia, mainly of allergic origin. Eosinophils were incubated with NGF (50 to 1000 ng/mL), and supernatants were collected for measurement of eosinophil peroxidase (EPO, 20 minutes, colorimetric enzymatic assay) and IL-6 (12 hours, ELISA). Eosinophil viability was evaluated by Trypan blue test (days 2, 3, and 4). NGF content in freshly isolated eosinophils, after ultrasound disruption, was determined with a 2-site immunoenzymatic assay. The presence of mRNA for NGF was evaluated by reverse transcription PCR. RESULTS NGF caused EPO release (highly significant at 1000 ng/mL NGF). IL-6 release from eosinophils was not higher than IL-6 spontaneously released into culture medium alone. NGF did not significantly affect the number of viable eosinophils. NGF was found in the eosinophil sonicates (1.5 to 17.8 pg/mL per 106 cells). Similarly, mRNA for NGF was detected by reverse transcription PCR in the freshly isolated eosinophils. CONCLUSIONS NGF activates human peripheral blood eosinophils from subjects with mild eosinophilia to selectively release inflammatory mediators. Eosinophils store and produce NGF. Therefore the capability of NGF to induce a secretory response and its production and storage by circulating human eosinophils suggest a possible role for NGF in conditions associated with eosinophilia, including allergic disease.

Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids.

PURPOSE To review the efficacy of inhibitors of matrix metalloproteinase-9, corticosteroids, and doxycycline for treatment of recalcitrant recurrent corneal erosion. METHODS Retrospective, clinic-based, interventional case series. The medical records of seven consecutive patients who were treated between January 1995 to January 2000 for recurrent corneal erosion who had not responded to conventional therapy were reviewed. Treatment of seven eyes of seven patients consisted of oral doxycycline (50 mg, two times a day) for 2 months along with a topical corticosteroid (either methylprednisolone 1%, prednisolone acetate 1%, or fluoromethalone 0.1%) three times a day, for 2 to 3 weeks. The effects of doxycycline and methylprednisolone on metalloproteinase-9 activity in human corneal epithelial cultures were evaluated by gelatin zymography and a commercial metalloproteinase-9 activity assay kit. RESULT Fingernail injury in three of the seven eyes was the most common form of corneal injury. There was no evidence of epithelial basement membrane or corneal stromal dystrophy in any of the patients, although epithelial microcysts were observed in the involved area in three patients. One eye had intact elevated corneal epithelium that showed abnormal diffuse staining with fluorescein dye, and six eyes had a corneal epithelial defect at the time of presentation. In all seven eyes, pain resolved and epithelial defects healed within 2 to 10 days after initiation of therapy. No recurrence was observed during an average follow-up period of 21.9 months (range, 1.5 to 60 months). Methylprednisolone and doxycycline each produced a statistically significant decrease in amount and activity of metalloproteinase-9 in conditioned media of human corneal epithelial cultures. CONCLUSIONS Therapy with a combination of medications that inhibit metalloproteinase-9 produced rapid resolution and prevented further recurrence of cases of recurrent corneal erosions that were unresponsive to conventional therapies.

Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers☆

PURPOSE To describe the clinical outcome of amniotic membrane transplantation (AMT) for nontraumatic corneal perforations, descemetoceles, and deep ulcers. DESIGN Retrospective, noncomparative, interventional case series. PARTICIPANTS Thirty-four eyes of 33 consecutive patients operated on for nontraumatic corneal perforations or descemetoceles at four academic departments of ophthalmology. Associated autoimmune disorders included rheumatoid arthritis (n = 6), Stevens-Johnson syndrome (n = 3), ocular cicatricial pemphigoid (n = 2), systemic lupus erythematosus (n = 1), and one eye with Moorens ulcer, as well as neurotrophic, or exposure keratopathy (n = 10), postinfectious nonhealing ulcers (n = 6), and postsurgery (n = 5). INTERVENTION Three or four layers of amniotic membrane (AM) were applied over the ulcer bed and anchored with 10-0 nylon interrupted or running sutures. A large AM piece was used as a patch to cover the entire corneal surface. MAIN OUTCOME MEASURES Formation of anterior chamber depth, epithelialization of the AM grafts, and stability of the corneal stromal thickness. RESULTS The mean follow-up period was 8.1 +/- 5.7 (ranging from 2-23) months. A successful result was observed in 28 of 34 eyes (82.3%). Of the successful cases, 23 eyes needed one AMT procedure, whereas 5 eyes needed two procedures to achieve a successful result. In five eyes, a subsequent definitive surgical procedure such as penetrating keratoplasty or lid surgery was needed. Failure was observed in six eyes with rheumatoid arthritis, neurotrophic keratopathy, or graft melting. CONCLUSIONS AMT is an effective method for managing nontraumatic corneal perforations and descemetoceles. It can serve as either a permanent therapy or as a temporizing measure until the inflammation has subsided and a definitive reconstructive procedure can be performed. This treatment option is also beneficial in those countries where corneal tissue availability is limited.

Amniotic membrane transplantation for reconstruction of the conjunctival fornices

PURPOSE To describe the clinical outcome of amniotic membrane transplantation (AMT) for fornix reconstruction in a variety of ocular surface disorders. DESIGN Noncomparative interventional case series. PARTICIPANTS Seventeen eyes in 15 patients with symblepharon. Four eyes had ocular-cicatricial pemphigoid, two eyes had symblepharon after pterygium excision, four eyes had chemical or mechanical trauma, two eyes had strabismus surgery, two eyes (one patient) had Stevens-Johnson syndrome, one eye had toxic epidermal necrolysis, and two eyes (one patient) had chronic allergic conjunctivitis. INTERVENTION The subconjunctival scar tissue was dissected from the episclera, and the freed conjunctival flap was recessed to the fornix. A layer of amniotic membrane (AM) was applied to cover the exposed episclera. The fornical edge of the membrane was anchored with sutures passing through the full thickness of the lid. MAIN OUTCOME MEASURES A deep conjunctival fornix, lack of motility restriction. RESULTS The mean follow-up period was 37 +/- 24 months (range, 9-84 months). Complete fornix reconstruction was demonstrated in 12 of 17 eyes (70.6%), whereas 2 eyes had a partial success, and 3 eyes (3 patients) had recurrence of symblepharon with restricted motility. In eyes that demonstrated partial success or failure, the underlying etiology was either an autoimmune disorder or a recurrent pterygium. The most successful outcome was observed in eyes with symblepharon associated with trauma. CONCLUSIONS AMT is an effective method of fornix reconstruction for the repair of symblepharon in a variety of ocular surface disorders. Future modifications, including an epithelial cellular component on the AM (conjunctival autograft or ex vivo expanded epithelial stem cells) may improve the outcome of this surgical procedure.

Amniotic membrane transplantation for reconstruction after excision of large ocular surface neoplasias

Aim: To evaluate the clinical outcome of patients in whom ocular surface reconstruction was performed using amniotic membrane transplantation (AMT) after the excision of large (>20 mm square) ocular surface neoplasias (OSN). Methods: A non-comparative interventional case series. In 16 eyes of 16 patients, excision of large OSN including conjunctival intraepithelial neoplasia (CIN), primary acquired melanosis, and malignant melanoma was followed by adjunctive cryotherapy and suturing of a single layer of amniotic membrane (AM) with the basement membrane side facing up to the healthy bordering tissue. Epithelial healing, complications, and tumour recurrences were analysed. Results: During a mean follow up of 23.7 (SD 11, range 11–43) months, ocular surface healing was rapid and complete in all cases. One complication of pyogenic granuloma was noted. Tumour recurrence occurred in one out of 10 CIN cases (10%), no recurrences were observed in the patients with melanotic lesions. Conclusions: AMT in lieu of conjunctival or mucosal autograft is an effective substrate for reconstructing the ocular surface following excision of large OSN. AMT is effective in managing large OSN by avoiding the complications that may be associated with conventional removal, specifically in cases where the limbal architecture is destroyed by surgical resection or adjuvant therapies.

Keratolimbal allograft in corneal reconstruction

AbstractThe replenishment of corneal epithelial SC is a crucial step for reconstructing the ocular surface in patients suffering from devastating ocular surface diseases manifesting with total LSCD. KLAL is one of such procedures and has a long track record and a long follow-up for patients with bilateral total LSCD. This review summarizes the literature experiences and outline new strategies that are important to enhance the success of this procedure. Further research is needed to fully understand the biological processes involved in allogeneic tissue transplantation for preserving epithelial SC adhesion, migration, and survival.

AMNIOTIC MEMBRANE TRANSPLANTATION FOR BULLOUS KERATOPATHY IN EYES WITH POOR VISUAL POTENTIAL

Purpose: To evaluate the long‐term outcomes of epithelial debridement and amniotic membrane transplantation (AMT) for pain and discomfort relief in patients with symptomatic bullous keratopathy and poor visual potential. Setting: Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA. Methods: This retrospective study included 18 eyes (18 patients) with bullous keratopathy presenting with intractable pain or discomfort and poor visual potential. After epithelial debridement, all eyes had AMT with the basement membrane side up. During a mean follow‐up of 25.1 months ± 9.6 (SD) (range 12 to 45 months), pain relief, epithelial healing, and visual changes were analyzed. Results: Pain relief was obtained in 88% of patients. Sixty‐six percent of eyes had complete resolution of ocular discomfort starting soon after the first postoperative day. One eye had evisceration for persistent pain 10 months postoperatively. Corneal epithelial healing was complete in all except 1 eye. Remaining complaints included foreign‐body sensation (5%), tearing (11%), and photophobia (5%). Conclusions: Amniotic membrane transplantation was a safe, effective, and long‐lasting treatment modality for intractable pain associated with chronic bullous keratopathy in eyes with poor visual potential. It can be an alternative to conjunctival flaps for the long‐term management of patients with bullous keratopathy in whom corneal transplantation is not indicated. A comparison of the efficacy of AMT with that of other surgical procedures must be performed.