Stephen C. Pflugfelder

Nosocomial Endophthalmitis Survey: Current Incidence of Infection after Intraocular Surgery

The authors reviewed the incidence of hospital-linked postoperative endophthalmitis at the Bascom Palmer Eye Institute between January 1, 1984 and June 30, 1989. After 30,002 intraocular surgical procedures, the following incidence of culture-proven endophthalmitis was observed: (1) extracapsular cataract extraction (ECCE) with or without intraocular lens (IOL) implantation--0.072% (17 of 23,625 cases); (2) pars plana vitrectomy--0.051% (1 of 1974 cases); (3) penetrating keratoplasty (PKP)--0.11% (2 of 1783 cases); (4) secondary IOL--0.30% (3 of 988 cases); and (5) glaucoma filtering surgery--0.061% (1 of 1632 cases). A statistically significant (P = 0.038, Fishers exact test, two-tailed) increased incidence of endophthalmitis occurred in diabetic (0.163%, 6 of 3686 cases) compared with nondiabetic (0.055%, 11 of 19,939 cases) patients undergoing ECCE with or without IOL implantation. The authors also reviewed the incidence of postoperative endophthalmitis after intracapsular cataract extraction (ICCE) with and without IOL and observed an incidence of 0.093% (7 of 7552) in cases operated on between September 1, 1976 and December 31, 1982.

Evaluation of subjective assessments and objective diagnostic tests for diagnosing tear-film disorders known to cause ocular irritation.

Purpose To determine which subjective assessments and objective tests have clinical utility as diagnostic tools in ocular irritation associated with Sjögrens syndrome—related aqueous tear deficiency (ATD), non-Sjögren ATD, inflammatory meibomian gland disease (MGD) associated with rosacea, and atrophic MGD. Methods Forty adults with ocular irritation and 10 with normal ocular surfaces were enrolled in a nonrandomized, nonblinded clinical trial. Symptoms were evaluated. Tests included biomicroscopy; evaluation of tear-film integrity, production, and clearance; fluorescein and rose bengal staining; and serum autoantibody screening. Results Symptoms were similar among groups and most severe in the Sjögrens group. Fluorescein tear break-up time was significantly faster in the ATD and MGD groups than that in controls. Schirmer scores were significantly lower in the ATD group than those in MGD and control groups. Tear clearance was delayed in the ATD and atrophic MGD groups. Xeroscope grid distortion was noted only with ATD. The Sjögrens group had greater loss of nasolacrimal reflex, slower fluorescein clearance, and greater ocular-surface fluorescein and rose bengal staining than did the others. More MGD subjects had meibomian gland orifice metaplasia and acinar dropout than did those with Sjögren-related ATD and controls. Schirmer scores correlated inversely with rose bengal staining, corneal fluorescein staining, and grid distortion. Rose bengal staining correlated with grid distortion and loss of nasal—lacrimal reflex, but not with MGD. Conclusion Subjective assessments and objective diagnostic tests have clinical utility as diagnostic tools in tear-film disorders. ATD is correlated with ocular-surface disease. An algorithm summarizing the diagnostic utility of these tests is included.

Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface

PURPOSE To evaluate components of the integrated ocular surface/lacrimal gland unit in a series of patients before and after undergoing bilateral laser in situ keratomileusis (LASIK). DESIGN Prospective, noncomparative case series. PARTICIPANTS Forty-eight eyes of 14 men and 34 women (age range, 26-54; mean, 39.2 years) who underwent bilateral LASIK for myopia or myopic astigmatism. METHODS LASIK was performed using a VISX Star Excimer Laser (Santa Clara, CA). Patients completed a questionnaire containing 11 questions that evaluated the character and severity of ocular irritation symptoms. Snellen visual acuity, tear fluorescein clearance, corneal fluorescein staining, aqueous tear production by the Schirmer 1 test, and corneal and conjunctival sensitivity were measured in each eye. Corneal surface regularity (SRI) was evaluated with the Tomey TMS-1 (Tomey, Cambridge, MA) topography instrument. Each randomly chosen eye was evaluated 1 to 2 days (T0) before LASIK and 7 days (T1), 1 (T2), 2 (T3), 6 (T4), 12 (T5), and 16 (T6) months postoperatively. A Wilcoxon test, two-tailed paired t test, Friedman test, or analysis of variance were used for statistical comparisons. MAIN OUTCOME MEASURES Components of the integrated ocular surface/lacrimal gland unit. RESULTS Both corneal and conjunctival sensitivity were noted to be significantly decreased from preoperative levels at 1week, 1 month, 12 months, and 16 months postoperatively (P < 0.0002 at each time point). Symptom severity scores were significantly increased at 1 week, 12 months, and 16 months postoperatively (P < 0.007 at all time points). The mean Schirmer 1 test scores were 24 +/- 14 mm preoperatively, and they decreased to 18 +/- 14 mm by 1 month postoperatively (P < 0.001). Tear fluorescein clearance showed a linear increase postoperatively and was significantly greater than baseline (P < 0.001) at each time point. There was a significant increase in punctate corneal fluorescein staining at 1 week postoperatively (P < 0.0001), but staining returned to baseline by 12 months. There was a statistically significant increase in SRI 1 week postoperatively (P < 0.007) with return to baseline levels by 6 months. CONCLUSIONS Sensory denervation of the ocular surface after bilateral LASIK disrupts ocular surface tear dynamics and causes irritation symptoms. Patients undergoing LASIK should be informed of these risks.

Correlation of Goblet Cell Density and Mucosal Epithelial Membrane Mucin Expression with Rose Bengal Staining in Patients with Ocular Irritation

PURPOSE This study was designed to compare goblet cell densities and mucosal epithelial membrane mucin (MEM) expression in impression cytology specimens obtained from control subjects and patients with one of the following clinically defined diseases: aqueous tear deficiency (ATD) associated with Sjögren syndrome, ATD not associated with Sjögren syndrome, inflammatory Meibomian gland disease associated with rosacea, and Meibomian gland atrophy. These data were correlated with ocular surface rose Bengal staining scores, Schirmer scores, and HLA-DR antigen staining of conjunctival epithelial cells. METHODS Goblet cell density and MEM expression were studied by impression imprints with immunohistochemical staining using an anti-mucosal epithelial membrane mucin antibody in the temporal and inferior bulbar and inferior tarsal conjunctiva of study subjects. RESULTS Goblet cell density adjacent to the temporal limbus was significantly reduced at 3 mm posterior to the temporal limbus in both aqueous tear deficiency groups compared with the other groups and in patients with Sjögren syndrome compared with all other groups. In the inferior tarsus, goblet cell density was significantly reduced in patients with non-Sjögren syndrome ATD as compared with all other groups, except those with inflammatory Meibomian gland disease. Mucosal epithelial membrane mucin expression in the bulbar and tarsal conjunctiva was absent in a greater percentage of patients with Sjögren syndrome compared with all other groups. Total ocular surface rose Bengal staining scores were significantly higher in patients with Sjögren syndrome as compared with all other groups and in patients with non-Sjögren syndrome ATD as compared with control groups. Rose Bengal staining scores and Schirmer I test results (without anesthesia) were inversely correlated with bulbar, but not tarsal, conjunctival goblet cell densities, and with the absence of bulbar conjunctival MEM expression. CONCLUSIONS These results suggest that reduced goblet cell density and mucosal epithelial cell mucin expression could explain increased rose Bengal staining in patients with aqueous tear deficiency. In addition, MEM may be regarded as a marker for normal differentiation of ocular surface epithelia, with its absence signifying the development of squamous metaplasia.

The effects of long-term contact lens wear on corneal thickness, curvature, and surface regularity

PURPOSE To evaluate the effect of long-term contact lens wear on corneal thickness, curvature, and surface regularity. DESIGN A prospective, clinic-based, case-control study. PARTICIPANTS A total of 40 eyes of 20 normal subjects and 64 eyes of 35 subjects wearing contact lenses for more than 5 years were evaluated. METHODS The Orbscan Corneal Topography System was used to evaluate the entire corneal thickness and curvature, anterior curvature and the anterior and posterior elevation topographic patterns in normal eyes and subjects wearing contact lenses on a regular basis for more than 5 years. Indices of TMS-1 Corneal Topography System were used to determine corneal surface regularity in subjects wearing contact lenses and normal eyes. All topographic examinations were performed after contact lenses had been removed for at least 2 weeks. MAIN OUTCOME MEASURES The entire corneal thickness, curvature, surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity (PVA) and topographic patterns were compared between normal eyes and subjects wearing contact lenses for more than 5 years. RESULTS The 64 eyes of 35 subjects evaluated by the Orbscan instrument had an average of 13.45 +/- 6.42 years of contact lens wear. The mean corneal thickness in the center and in eight peripheral areas measured in contact lens wearing subjects was significantly reduced by about 30 to 50 microm compared to normal subjects (P < 0.001 for central and peripheral sites). No correlation was noted between central corneal thickness and degree of myopia in diopters (r = 0.15, 0.10 < P < 0.25). The corneal curvature, maximum keratometry (Max K) and minimum keratometry (Min K) readings, were significantly steeper in eyes wearing contact lenses than normal eyes (P < 0.01 for Max K and Min K measured by both instruments). No difference in the mean corneal astigmatism was noted between groups. The SRI and SAI, but not the PVA index, of the TMS-1 were significantly greater in contact lens wearers than in the control group (P < 0.01 for both SRI and SAI, P = 0.15 for PVA). The color-coded patterns of all curvature and elevation maps made with both instruments showed no significant difference between subjects wearing contact lenses and the control group. There was no significant difference between corneal curvature measurements taken with the Orbscan System or the TMS-1 System in both normal and contact lens groups. CONCLUSIONS Long-term contact lens wear appears to decrease the entire corneal thickness and increase the corneal curvature and surface irregularity.

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.

Exogenous Fungal Endophthalmitis

The authors report 19 cases of exogenous fungal endophthalmitis managed between 1969 and 1986. These developed after ocular surgery (5 cases), after trauma (6 cases), by intraocular spread from fungal keratitis (4 cases), after therapeutic keratoplasty for keratitis (3 cases), and by spontaneous infection of a filtration bleb (1 case). The diagnosis of endophthalmitis was made from 3 days to 4 months after surgery or trauma. In patients with preexisting keratitis, endophthalmitis was noted 2 weeks to 5 months after the onset of keratitis. Seventeen cases were caused by filamentous fungi; two were caused by yeast. Fusarium (6 cases) and Acremonium (3 cases) accounted for approximately one half of the isolates. Forty-two percent of the patients recovered 20/400 or better acuity (3 of 5 postoperative cases, 4 of 6 trauma cases, and 1 of 4 keratitis cases). The clinical and microbiologic features of these cases are presented, and recommendations for management are offered.

Corneal surface regularity and the effect of artificial tears in aqueous tear deficiency

PURPOSE To evaluate corneal surface regularity and the effect of artificial tears on the regularity of the corneal surface in dry eye. DESIGN A prospective, clinic-based, case-control study. PARTICIPANTS A total of 64 eyes of 33 normal subjects and 42 eyes of 22 patients with aqueous tear deficiency were evaluated. METHODS Indices of the TMS-1 corneal topography instrument (Tomey Technology, Cambridge, MA) were used to evaluate corneal surface regularity and potential visual acuity (PVA) in patients with aqueous tear deficiency dry eye before and after the instillation of artificial tears and in normal subjects. The TMS-1 topographic maps were classified into round, oval, symmetric bow-tie, asymmetric bow-tie, and irregular patterns. MAIN OUTCOME MEASURES The surface regularity index (SRI), surface asymmetry index (SAI), PVA index, and topographic pattern of the TMS-1 were compared between normal and dry eyes and in dry eyes before and after the instillation of artificial tears. RESULTS The SRI and SAI were significantly elevated and the PVA was significantly reduced in dry eye patients compared with normal subjects: 0.31+/-0.22, 0.30+/-0.16, and 20/17.89+/-20/3.04, respectively, in normal subjects and 1.28+/-0.73, 1.05+/-1.17, and 20/33.45+/-20/13.99, respectively, in patients with dry eye (P<0.001 for all indices). The average amount of astigmatism was also increased in dry eyes (2.10+/-1.96 prism diopters) compared with normal eyes (1.13+/-0.53 prism diopters, P = 0.02). In dry eyes, the SRI and SAI were positively correlated with corneal fluorescein staining scores (P = 0.005 for SRI and P = 0.016 for SAI). The mean PVA was not significantly different from the mean actual corrected visual acuity. The dry eyes had a significantly lower percentage of symmetric bow-tie patterns and a greater percentage of irregular patterns on topographic maps than normal eyes. After the instillation of artificial tears, the SRI, SAI, and mean astigmatism all decreased significantly (P<0.001 for SRI, P<0.002 for SAI, P = 0.04 for astigmatism) and the PVA improved (P<0.001) in dry eyes. An irregular topographic pattern was observed in 45.24% of dry eyes, and this decreased to 30.95% after the instillation of artificial tears (P<0.005). CONCLUSIONS Patients with aqueous deficiency have an irregular corneal surface that may contribute to their visual difficulties. The SRI and SAI could be used as objective diagnostic indices for dry eye as well as for evaluating the severity of this disease and the effect of artificial tears. Artificial tears have the secondary benefit of smoothing the corneal surface in dry eye.

Conjunctival Cytologiec Features of Primary Sjögren's Syndrome

Abstract To determine whether there are specific cytologic features associated with primary Sjogrens syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB ( P 75%) goblet cell loss of the TB ( P P P P

Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

Purpose. To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. Methods. Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. Results. There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. Conclusions. This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.