Impaired memory and learning abilities in patients with systemic lupus erythematosus as measured by the Rey Auditory Verbal Learning Test.

OBJECTIVE: The purpose of this study was to assess and characterise verbal memory impairment in patients with systemic lupus erythematosus (SLE) by the Rey Auditory Verbal Learning Test (Rey AVLT). METHODS: 40 consecutive, unselected patients with SLE were evaluated with the Rey AVLT, a clinical and research tool for the study of multiple learning and memory measures. All patients were assessed for disease activity, damage, presence of antiphospholipid antibodies and depression. Findings were compared with those of 40 healthy controls matched for age, sex and education. RESULTS: The study group included 40 patients with SLE (37 females, 3 males), median age 33 years (range 20-59), median disease duration 8 years (range 0.3-32). The median disease activity measured by the SLE Disease Activity Index (SLEDAI) was 4 (range 0-16). Median damage measured by the SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) damage index score was 0 (range 0-4). Depression was detected in 16/40 patients. Several aspects of the memory domain, as measured by the Rey AVLT, were impaired in the SLE group, using analysis of variance with repeated measures. The learning curve of patients with SLE was significantly less steep compared with that of controls, (p = 0.036), the rate of words omitted from trial to trial was higher in the SLE group (p = 0.034) and retrieval was less efficient in SLE compared with controls (p = 0.004). The significance of these findings was maintained after omitting patients with stroke or depression. CONCLUSION: Learning ability was impaired in patients with SLE with a poor and inefficient learning strategy, as reflected by an impaired learning curve, repeated omissions and impaired retrieval. This pattern of memory deficit resembles that seen in patients with frontal lobe damage and warrants further localising brain studies.

Scleral perforation during retrobulbar and peribulbar anesthesia: risk factors and outcome in 50,000 consecutive injections.

PURPOSE: To measure the frequency of scleral perforation and identify related risk factors during local anesthetic injection for intraocular surgery. SETTING: Multispecialty eye hospital. METHODS: All patients (n = 50,000) having retrobulbar (26,857) or peribulbar (23,143) injections at the King Khaled Eye Specialist Hospital were reviewed. Cases of scleral perforation were analyzed for potential technical and ophthalmic risk factors, management of injuries, and visual and anatomic outcomes. Mean follow-up was 14.4 months (range 8 to 24 months). RESULTS: Seven (0.014%) needlestick injuries were identified, all of which had posterior staphyloma as the only identifiable risk factor. Applying a previously measured prevalence of 10.7% for posterior staphyloma in our surgery patients gave a scleral perforation rate of 0.13% (7 of 5350) for staphylomatous eyes. All perforated globes had originally planned cataract extraction within 8 weeks of injury. Additional management consisted of observation (2 cases), cryotherapy (2 cases), and vitreoretinal procedures for retinal detachment (3 cases) and subretinal hemorrhage (1 case). At last follow-up, all retinas were attached and 3 cases (42.8%) had a visual acuity of worse than 20/160. Both cases requiring multiple retinal detachment surgeries developed proliferative vitreoretinopathy and poor visual acuity. CONCLUSIONS: Eyes with posterior staphyloma sustained needlestick injuries at a rate of 1 in 760 compared with 0 injection perforations in more than 44,000 nonstaphylomatous eyes.

Outcome of cataract surgery associated with posterior staphyloma.

PURPOSE: To assess the outcome of cataract surgery in eyes with posterior staphyloma and identify predictors of surgical success. SETTING: Tertiary care referral center. METHODS: A retrospective analysis was conducted of 107 consecutive patients with posterior staphyloma and 107 control patients who had cataract surgery. Potential associations of preoperative variables with surgical success were analyzed using the chi-square test, multivariate linear regression, and Student t test. RESULTS: The staphyloma group was younger, had more women, and had a lower mean visual acuity preoperatively than the control group. All patients in the control group and all but 1 in the staphyloma group had intraocular lens (IOL) implantation at the time of cataract extraction. The rates of posterior capsule tear and vitreous loss were similar in the staphyloma and control groups. There was 1 case each of retinal detachment and IOL dislocation in the staphyloma group. The staphyloma group had significantly lower postoperative visual acuity than the control group; however, the percentage in the staphyloma group with a visual acuity of finger counting or worse decreased from 80.4% preoperatively to 16.8% postoperatively and the percentage with an uncorrected visual acuity of 20/160 or better increased from 5.6% to 67.3%. Myopic degeneration was judged to be the cause of postoperative acuity worse than 20/100 in 22.4% in the staphyloma and 0% in the control group; other causes for poor postoperative acuity were similar in the 2 groups. In the staphyloma but not the control group, decreased postoperative acuity was independently associated with age greater than 65 years and axial length greater than 29.0 mm. CONCLUSIONS: Myopic degeneration may limit the results of cataract extraction in up to one fourth of patients with posterior staphyloma. Nevertheless, a substantial improvement in mean visual acuity resulted that was not associated with a significant increase in surgical complications.

Axial length and posterior staphyloma in Saudi Arabian cataract patients.

PURPOSE: To determine the axial length distribution and prevalence of posterior staphyloma in a group of Saudi Arabian patients having cataract extraction. SETTING: Tertiary care referral center. METHODS: Approximately 75% of all cataract patients at the eye hospital have preoperative B-scan ultrasonography. The last 1000 B-scans performed for any reason were screened for patients having uncomplicated cataract surgery; 629 cases were included. The relationship between the presence of posterior staphyloma and patient age, sex, and axial length was studied. RESULTS: There were 371 (59.0%) men and 258 (41.0%) women with a mean age of 62.4 years +/- 15.7 (SD). Posterior staphyloma was identified in 67 patients (10.7%). The presence of staphyloma was not significantly related to patient sex or age. Although the mean axial length was significantly longer in eyes with staphyloma (27.43 +/- 2.36 mm) than in those without (23.18 +/- 1.64 mm), 9.3% of eyes without staphyloma had an axial length longer than 25.0 mm. No staphylomas were present in eyes with an axial length shorter than 23.3 mm. The longest axial length in an eye without a staphyloma was 32.5 mm. CONCLUSIONS: Posterior staphyloma was present in a high percentage of Saudi Arabian patients having cataract extraction.

Expulsive iridodialysis: an isolated injury after phacoemulsification.

I report a case of blunt trauma to an eye that had had uneventful phacoemulsification through a 5.0 mm self-sealing corneoscleral incision 4 months earlier. Total iris expulsion occurred through the cataract incision without extension of the wound or disruption of the posterior capsule or intraocular lens. A possible mechanism for this injury is discussed and related to the unique properties of the corneoscleral incision.

Topography after repair of full-thickness corneal laceration.

PURPOSE: To characterize corneal topography after repair of full-thickness corneal laceration. SETTING: Ophthalmic emergency room serving as a trauma referral center. METHODS: Twenty-two eyes with full-thickness corneal lacerations were prospectively studied after standardized surgical repair. Computerized videokeratography was done 2 and 14 weeks after surgery, with the latter measurement corresponding to 6 to 8 weeks after all sutures were removed. Fellow uninjured eyes served as the control group. RESULTS: Twenty eyes (91%) had a significant reduction in topographic distortion after suture removal. Mean corneal astigmatism, measured by simulated keratometry, was 10.70 diopters (D) +/- 5.90 D (SD) with sutures in place and 2.25 +/- 4.90 D after their removal (P < .005). Eighteen patients (82%) had 2.00 D or less of corneal astigmatism 6 to 8 weeks after all sutures were removed. The final distribution of topographic patterns was bow tie (50%), spherical/oval (36%), and irregular (14%). There was no significant correlation between laceration configuration (curvilinear, jagged, branched wound margins) and final topography. Lacerations that passed within 2.0 mm of the line of sight, however, were significantly more likely to have more than 2.00 D of final astigmatism. Mean central corneal power was 42.40 +/- 3.20 D in the injured eyes and 42.40 +/- 2.40 D in the uninjured fellow eyes. CONCLUSION: Although high astigmatism is frequently produced by corneal sutures used to repair full-thickness lacerations, the cornea has a substantial topographic memory that results in a marked normalization of contour after suture removal.

Expression of cell cycle-associated proteins in human and rabbit corneal endothelium in situ.

PURPOSE: It is unknown why human corneal endothelium exhibits limited capacity to divide while the endothelia of other species, such as rabbit, divide in vivo at wounding and in culture. A potentially valuable source of information concerning why human endothelium has such a limited proliferative capacity lies in elucidating any differences in the molecular events governing the cell cycle of these two species. A recent study of the relative expression of cell cycle-associated proteins in donor corneas suggests that human corneal endothelial cells in vivo have not exited the cell cycle but are arrested in G1-phase. The purpose of the current study was to identify differences in cell cycle protein expression in human and rabbit endothelium that would explain the difference in their relative proliferative capacities. Specifically, the authors first ascertained the relative proliferative status of rabbit corneal endothelial cells in vivo. The expression and intracellular distribution of G1-phase regulatory proteins was then determined in both species, and the results were compared. METHODS: Corneas from New Zealand white rabbits (weight range, 2 to 3 kg) and from human donors (age range, 6 months to 67 years) were fresh frozen, cryostat sectioned, and prepared for indirect immunofluorescence microscopy using an established protocol. The following monoclonal antibodies were localized in rabbit corneal endothelium only: cyclins D, E, A, and B1; protein kinase p34cdc2; and Ki67, a marker of actively cycling cells. Localization patterns for the following G1-phase regulatory proteins were compared in both human and rabbit corneal endothelia: the tumor suppressors, pRb, p53, and p16INK4, and the transcription factor, E2F. Reverse transcription-polymerase chain reaction studies were conducted to detect mRNA for Ki67 in human and rabbit corneal cells. RESULTS: Cyclins D, E, and A were localized in the cytoplasm of rabbit corneal endothelium, whereas cyclins B1 and p34cdc2 were detected in the nucleus. No Ki67 protein or mRNA expression was detected in the endothelium of either species. In human and rabbit endothelia, p53 and p16INK4 were localized to the cytoplasm, whereas pRb was detected in the nucleus. E2F exhibited a nuclear and a cytoplasmic localization in each species. CONCLUSIONS: The corneal endothelium of rabbits stained positively for cyclins D, E, and A and did not stain for Ki67, suggesting that, as in humans, rabbit corneal endothelium in vivo is arrested in G1-phase upstream from Ki67 synthesis. Cyclin E was located in the cytoplasm of rabbit cells, whereas it was found in the nucleus in human endothelium. The apparent difference in cellular distribution of cyclin E in these two species may be significant because this cyclin is active during the G1-/S-phase transition. It is possible that in situ human and rabbit corneal endothelial cells are arrested at different points within G1-phase and/or that the difference in relative proliferative capacity exhibited by the corneal endothelium in these two species may be caused by differences in their relative ability to overcome G1-phase arrest.

Computerized topography of a full-thickness corneal laceration.

A full-thickness corneal laceration was studied by computerized topography. Measurements taken preoperatively and during healing allowed the effects of the injury, its repair, and subsequent suture removal to be isolated and separately analyzed.

Characterization of a phosphodiesterase-immunoreactive polypeptide from rod photoreceptors of developing rd mouse retinas.

In the inherited retinal degeneration of rd mice, cyclic GMP accumulates in affected rod photoreceptors prior to their degeneration. A deficiency in the activity of the visual cell phosphodiesterase apparently results in the accumulation of cyclic GMP. The cyclic GMP phosphodiesterase (PDE) of normal mouse photoreceptors is a heteromeric protein complex of about 170 kDa, consisting of the alpha beta catalytic unit and the gamma inhibitory unit. The isolated complex has low enzyme activity but it can be activated by incubation with histone. Affinity-purified polyclonal antibodies against the PDE complex of bovine rod outer segments were prepared and used to identify in retinas of both normal and rd mice PDE-immunoreactive polypeptides which comigrated on SDS-polyacrylamide gels with the large subunits (88 kDa) of the normal PDE complex. During development of normal retinas, the 88 kDa immunoreactive component of the PDE complex were detected by day 7, with immunoreactivity increasing throughout the second postnatal week. In rd retinas, the 88 kDa immunoreactivity increased after 9 postnatal days, decreased during rod photoreceptor degeneration, and was undetectable in mature rd retinas. Under nondenaturing conditions, the PDE-immunoreactive polypeptide of rd retinas sedimented on sucrose gradients with a sedimentation coefficient of 5.6S and an apparent molecular mass of about 105 kDa; no associated histone-activated PDE activity was detected. These findings show that PDE-immunoreactive polypeptides are synthesized in immature rd photoreceptors and that the PDE-immunoreactive polypeptides fail to form a PDE complex which is comparable to that of normal photoreceptors.

Characterization of transducin from bovine retinal rod outer segments. Use of monoclonal antibodies to probe the structure and function of the subunit.

A panel of monoclonal antibodies has been developed against the T alpha, T beta and T gamma subunits of bovine transducin. Two anti-T alpha antibodies from this panel (TF15 and TF16) and a third one (4A) against frog T alpha (Witt, P. L., Hamm, H. E., and Bownds, M. D. (1984) J. Gen. Physiol. 84, 251-263) were characterized. Each of these monoclonal antibodies recognizes a different region of T alpha and has a specific effect on the function of transducin. The binding of TF15 is reversibly enhanced by treating T alpha with either 1 M guanidinium chloride or, to a smaller extent, by the removal of bound guanine nucleotide. Its epitope is located in a 12-kDa tryptic fragment containing the binding site for the guanine moiety of GTP. Taken together, these results support previous observations that the conformation of T alpha is modulated by the occupancy of the guanine nucleotide binding site. In contrast to TF15, TF16 recognizes only the native form of T alpha. Its epitope resides within the central portion of the T alpha molecule. While T alpha-bound TF16 does not inhibit either pertussis toxin-catalyzed ADP-ribosylation, rhodopsin binding, or transducin subunit interaction, it blocks both the light-activated uptake of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and the GTP-dependent elution of transducin from photolyzed rhodopsin. These effects are unlikely to be caused by the occupation of the guanine nucleotide binding site by TF16 because this antibody quantitatively precipitates T alpha-GTP gamma S. We propose that bound TF16 locks T alpha in a conformation that prevents the entrance of guanine nucleotide and favors T beta gamma association. In contrast to TF16, the epitope of 4A was mapped to the amino-terminal region of T alpha. This monoclonal antibody blocks pertussis toxin-catalyzed ADP-ribosylation, GTP gamma S uptake, and T alpha-T beta gamma association. Moreover, the binding site for 4A becomes inaccessible when transducin binds to photolyzed rhodopsin. These results suggest that the inhibitory effects of 4A are due to a simultaneous steric blockage of both the interaction of T alpha with T beta gamma and their binding to photolyzed rhodopsin. The results obtained from these studies are correlated with the structure and function of T alpha.

Characterization of transducin from bovine retinal rod outer segments. Participation of the amino-terminal region of T alpha in subunit interaction.

The GTP-induced dissociation of T alpha from T beta gamma initiates the release of transducin from photolyzed rhodopsin and the subsequent activation of the cGMP phosphodiesterase. In this study, site-specific proteolysis and immunoprecipitation were used to map the domain of T alpha that interacts with T beta gamma. We found that Staphylococcus aureus V8 protease rapidly removes a small fragment from T alpha under native conditions, resulting in the formation of a single 38-kDa polypeptide (T alpha'). Under the same conditions, T beta gamma remains intact. A 4.5-fold decrease in the rate of T alpha cleavage by S. aureus protease was observed in the presence of T beta gamma, suggesting T beta gamma binding blocks the protease-sensitive site on T alpha. Amino acid sequence analysis indicated that T alpha' is derived from the cleavage of T alpha at Glu-21. The ability of T alpha' to interact with and activate the retinal phosphodiesterase is not diminished. However, T alpha' is unable to participate in T beta gamma-dependent activities such as the light-stimulated binding of guanine nucleotides, binding to photoexcited rhodopsin, and ADP-ribosylation catalyzed by pertussis toxin. Moreover, the anti-T alpha monoclonal antibody TF16 was able to precipitate T beta gamma in the presence of T alpha, but not with either T alpha' or T alpha-guanosine 5'-O-(3-thiotriphosphate). We conclude that the amino-terminal region of T alpha participates in T beta gamma interaction and discuss our results with respect to the known structure and function of transducin.

Infection of neuroretinal cells in vitro by avian sarcoma viruses UR1 and UR2: transformation, cell growth stimulation, and changes in transducin levels.

Infection in vitro of differentiating chick embryo neuroretinal cells with avian sarcoma viruses UR1 and UR2 results in mitogenic stimulation and morphologic conversion of both support neuronal cells. This was shown by the continuous propagation of transformed cells for over 4 months and growth of reaggregated colonies in liquid medium as well as in soft agar. Production of the transforming proteins p 150 gag-fps and p68 gag-ros of UR1 and UR2, respectively, was similar to that of transformed chick embryo fibroblasts, as judged from in vitro kinase activity assays. The two protein subunits, T beta and T gamma, but not T alpha of the GTP binding protein transducin, found in the retina of many animal species, were present in control neuroretinal cells. Infection with Rous sarcoma virus or UR2 resulted in an inhibition of T gamma synthesis and enhancement of T beta-like protein production.