Ajay E. Kuriyan

The eye and thyroid disease.

Purpose of review The pathophysiology and optimal management of thyroid eye disease (TED) have not yet been elucidated. Recent studies have increased our knowledge of the disease process and different diagnostic and therapeutic options. This review highlights the recent progress in TED research and identifies areas requiring further advancements. Recent findings The pathophysiology of TED likely involves genetic and environmental factors, which may potentiate cellular and humoral-mediated inflammation within the orbit. Despite progress in TED research, a target antigen has not been established with certainty. New diagnostic methods and questionnaires are being developed that potentially provide information regarding inflammatory activity of TED. Corticosteroids alone or in combination with orbital radiation may be effective in improving TED symptoms. New immunomodulating therapies may also have a role TED management. Surgery is highly effective for treatment of TED-induced optic nerve compression and for managing the chronic soft tissue changes of TED. Summary A unifying hypothesis of TED pathophysiology is elusive. Further bench research into the autoimmune process is needed. In addition, large, prospective, randomized clinical trials based on the inflammatory activity of disease, while difficult to design, are essential to develop a consensus regarding the proper timing and use of anti-inflammatory medications.

Endophthalmitis Caused by Streptococcal Species: Clinical Settings, Microbiology, Management, and Outcomes

PURPOSE To report the clinical settings, antibiotic susceptibilities, and outcomes of endophthalmitis caused by Streptococcus species. DESIGN Retrospective, observational case series. METHODS Single-center study evaluating all patients with culture-positive endophthalmitis caused by Streptococcus species between January 1, 2000, and December 31, 2011. RESULTS Study criteria were met by 63 patients. The most common clinical settings were bleb associated (n = 17; 27%), after intravitreal injection (n = 16; 25%), and after cataract surgery (n = 13; 21%). The isolates were Streptococcus viridans (n = 47; 71%), Streptococcus pneumoniae (n = 13; 21%), and β-hemolytic Streptococci (n = 5; 8%). Sixty (95%) of 63 isolates were susceptible to vancomycin, 47 (98%) of 48 isolates were susceptible to ceftriaxone (third-generation cephalosporin), and 57 (93%) of 61 isolates were susceptible to levofloxacin (third-generation fluoroquinolone). Between the first and second half of the study, the minimal inhibitory concentration of antibiotics required to inhibit 90% of isolates increased by 1.5-fold for ceftriaxone and 2-fold for levofloxacin and remained the same for vancomycin. Initial treatment was vitreous tap (49; 78%) or pars plana vitrectomy (14; 22%); all received intravitreal antibiotics. Visual acuity outcomes were variable: best-corrected visual acuity was 20/400 or better in 16 (25%) patients and worse than 20/400 in 47 (75%) patients. Evisceration or enucleation was performed in 16 (25%) patients. CONCLUSIONS Streptococcus isolates generally had high susceptibility rates to commonly used antibiotics. Higher antibiotic minimal inhibitory concentrations were required to inhibit 90% of isolates in vitro in the second half of the study period compared with the first half. Despite prompt treatment, most patients had poor outcomes.

Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections.

BackgroundThe purpose of the current study was to analyze risk factors, clinical features, and treatment outcomes in patients with endogenous fungal endophthalmitis with yeast and mold infections. For this retrospective consecutive case series, microbiologic and clinical records were reviewed to identify all patients with intraocular culture-proven endogenous fungal endophthalmitis treated at a single institution between January 1, 1990 and December 31, 2011.ResultsSixty-seven eyes of 53 patients were identified; 51 eyes of 39 patients had positive cultures for yeast and 16 eyes of 14 patients had positive cultures for molds. Patients with molds as a causative organism had significantly shorter duration of symptoms prior to diagnosis (molds 3.8 days, yeast 21.0 days, p = 0.002), were more likely to be receiving iatrogenic immunosuppression (molds 57.1%, yeast 7.7%, p = 0.001), have a history of whole-organ transplantation (molds 35.7%, yeast 2.6%, p = 0.001), and were more likely to have hypopyon at the time of diagnosis (molds 37.5%, yeast 6.0%, p = 0.001). Patients with endogenous endophthalmitis caused by molds had significantly worse visual acuity at the time of diagnosis (logMAR visual acuity molds 1.80, yeast 1.15, p = 0.008) and at final visit (logMAR visual acuity molds 1.97, yeast 1.05, p = 0.005) compared to those patients with yeast as a causative organism. There was no significant difference in the rate of retinal detachment between the two groups (mold 12.5%, yeast 30.6%, p = 0.201). Patients with cultures positive for mold were significantly more likely to undergo enucleation (molds 25.0%, yeast 0%, p < 0.001).ConclusionsSystemic risk factors for patients with endogenous fungal endophthalmitis caused by molds were iatrogenic immunosuppression and a history of whole-organ transplantation. Shorter duration of symptoms before diagnosis and higher rates of hypopyon occurred in mold cases. While endogenous fungal endophthalmitis is generally associated with poor visual acuity outcomes, infection with mold species was associated with worse visual acuity on presentation and on final follow-up than infection with yeast species. Enucleation rates were much higher in mold cases.

Orbital fibroblasts from thyroid eye disease patients differ in proliferative and adipogenic responses depending on disease subtype.

PURPOSE Thyroid eye disease (TED) patients are classified as type I (predominantly fat compartment enlargement) or type II (predominantly extraocular muscle enlargement) based on orbital imaging. Orbital fibroblasts (OFs) can be driven to proliferate or differentiate into adipocytes in vitro. We tested the hypothesis that type I OFs undergo more adipogenesis than type II OFs, whereas type II OFs proliferate more than type I OFs. We also examined the effect of cyclooxygenase (COX) inhibitors on OF adipogenesis and proliferation. METHODS Type I, type II, and non-TED OFs were treated with transforming growth factor-beta (TGFβ) to induce proliferation and with 15-deoxy-Δ(-12,14)-prostaglandin J2 (15d-PGJ2) to induce adipogenesis. Proliferation was measured using the [(3)H]thymidine assay, and adipogenesis was measured using the AdipoRed assay, Oil Red O staining, and flow cytometry. The effect of COX inhibition on adipogenesis and proliferation was also studied. RESULTS Type II OFs incorporated 1.7-fold more [(3)H]thymidine than type I OFs (P < 0.05). Type I OFs accumulated 4.8-fold more lipid than type II OFs (P < 0.05) and 12.6-fold more lipid than non-TED OFs (P < 0.05). Oil Red O staining and flow cytometry also demonstrated increased adipogenesis in type I OFs compared to type II and non-TED OFs. Cyclooxygenase inhibition significantly decreased proliferation and adipogenesis in type II OFs, but not type I OFs. CONCLUSIONS We have demonstrated that OFs from TED patients have heterogeneous responses to proproliferative and proadipogenic stimulators in vitro in a manner that corresponds to their different clinical manifestations. Furthermore, we demonstrated a differential effect of COX inhibitors on type I and type II OF proliferation and adipogenesis.

Optical coherence tomography measurements of choroidal thickness in healthy eyes: Correlation with age and axial length

BACKGROUND AND OBJECTIVE To evaluate subfoveal choroidal thickness (CT) in healthy eyes using spectral-domain optical coherence tomography (SD-OCT) and provide correlations between age and axial length. PATIENTS AND METHODS Enhanced depth SD-OCT imaging was performed with Cirrus (Carl Zeiss Meditec, Dublin, CA) and Spectralis (Heidelberg Engineering, Heidelberg, Germany) instruments. CT was measured from the outer limit of the retinal pigment epithelium to the inner surface of the sclera. RESULTS The study enrolled 155 patients, with at least 20 in each decade between 22 and 89 years old. Mean axial length was 23.6 mm. Mean Heidelberg subfoveal CT was 286 µm. The correlation between Heidelberg and Zeiss subfoveal CT measurements was strong (r = .978) and significant (P < .001). Mean subfoveal CT was 7.7 µm thinner by Heidelberg versus Cirrus (P < .001). Multiple linear regression analysis revealed that age (P < .001), axial length (P = .001), and sex (P = .025) were significantly related to Heidelberg subfoveal CT. CONCLUSION There is a strong negative correlation between CT and age (P <.001), with a 25 µm decrease in CT for each decade of life. Increasing axial length demonstrated a negative correlation with CT, decreasing 24.9 µm for each mm of axial length. Future studies of CT measurements can be performed on either instrument and must account for axial length, age, and sex to make appropriate conclusions.

Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility: Literature review and options for treatment

Background Endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or resistance is an important clinical issue worldwide. Purpose To review the published literature on endophthalmitis caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance. Methods The data were analysed from a PubMed search of endophthalmitis cases caused by Gram-positive organisms with reported reduced vancomycin susceptibility and/or vancomycin resistance from 1990 to 2015. Results From 18 publications identified, a total of 27 endophthalmitis cases caused by Gram-positive organisms with reduced vancomycin susceptibility and/or vancomycin resistance were identified. The aetiologies of endophthalmitis were exogenous in 19/27 cases (11 post-cataract surgery, 2 post-penetrating keratoplasty, 1 post-glaucoma surgery, 4 post-open globe injury, 1 post-intravitreal injection of ranibizumab), and endogenous in 4/24 cases; no details were available about the four remaining patients. The causative organisms included Enterococcus species (7/27), coagulase-negative staphylococci (4/27), Staphylococcus aureus (4/27), Bacillus species (4/27), Streptococcus species (3/27), Leuconostoc species (3/27), Staphylococcus hominis (1/27), and unidentified Gram-positive cocci (1/27). Visual acuity of 20/400 or better at the final follow-up was recorded in 10/26 patients (38.5%; data were not available for one patient). Treatment options include fluoroquinolones, penicillin, cephalosporins, tetracyclines, and oxazolidinones. Conclusions In the current study, visual acuity outcomes were generally poor. Enterococcus and Staphylococcus species were the most common organisms reported and postoperative endophthalmitis after cataract surgery was the most common clinical setting.

Endophthalmitis Caused by Enterococcus faecalis: Clinical Features, Antibiotic Sensitivities, and Outcomes

PURPOSE To report the clinical features, antibiotic sensitivities, and visual acuity outcomes of endophthalmitis caused by Enterococcus faecalis. STUDY DESIGN Retrospective, observational case series. METHODS A consecutive case series of patients with culture-positive endophthalmitis caused by E. faecalis between January 1, 2002, and December 31, 2012, at an academic referral center. RESULTS Of 14 patients identified, clinical settings included bleb association (n = 8), occurrence after cataract surgery (n = 4), and occurrence after penetrating keratoplasty (n = 2). All isolates were vancomycin sensitive. When comparing isolates in the current study with isolates from 1990 through 2001, the minimal inhibitory concentration required to inhibit 90% of isolates increased for ciprofloxacin (4 μg/mL from 1 μg/mL), erythromycin (256 μg/mL from 4 μg/mL), and penicillin (8 μg/mL from 4 μg/mL), indicating higher levels of resistance. The minimal inhibitory concentration required to inhibit 90% of isolates remained the same for vancomycin (2 μg/mL) and linezolid (2 μg/mL). Presenting visual acuity ranged from hand movements to no light perception. Initial treatment strategies were vitreous tap and intravitreal antibiotic injection (n = 12) and pars plana vitrectomy with intravitreal antibiotic injection (n = 2). Visual acuity outcomes were 20/400 or worse in 13 (93%) of 14 patients. CONCLUSIONS Although all isolates were sensitive to vancomycin and linezolid, higher minimal inhibitory concentration required to inhibit 90% of isolates in the current study, compared with isolates from 1990 through 2001, occurred with ciprofloxacin, erythromycin, and penicillin. Despite prompt treatment, most patients had poor outcomes.

Association Between Subfoveal Choroidal Thickness, Reticular Pseudodrusen, and Geographic Atrophy in Age-Related Macular Degeneration

BACKGROUND AND OBJECTIVE To compare subfoveal choroidal thickness (CT) measurements in eyes with nonexudative age-related macular degeneration (AMD) in the presence or absence of reticular pseudodrusen (RPD). PATIENTS AND METHODS Subfoveal CT measurements obtained from patients with AMD enrolled in the COMPLETE study (30 drusen-only eyes and 30 eyes with geographic atrophy [GA]) were compared with an age-distributed normal control group. Multimodal images were evaluated to detect the presence of RPD. RESULTS After controlling for age and axial length, the mean CT was significantly thinner in the GA group with RPD (213.7 ± 53.1 µm) than in the GA group without RPD (335.3 ± 123.2 µm; P = .001). The mean CT in the GA group without RPD was not statistically different from the mean CT in the normal control group (P = .076) or the drusen group without RPD (P = .45). In eyes without RPD, there was a correlation between the increasing size of GA and a decrease in CT measurements. CONCLUSION Subfoveal choroidal thinning in eyes with nonexudative AMD was associated with the presence of RPD. In the absence of RPD, CT only decreased as the size of GA increased.

ENDOPHTHALMITIS CAUSED BY PSEUDOMONAS AERUGINOSA: Clinical Features, Antibiotic Susceptibilities, and Treatment Outcomes.

Purpose: To report the clinical features, antibiotic susceptibilities, and visual outcomes associated with endophthalmitis caused by Pseudomonas aeruginosa. Methods: A consecutive case series. Microbiology database records were retrospectively reviewed for all patients with endophthalmitis caused by P. aeruginosa from January 1, 2002, to December 31, 2012, at a large university referral center. The corresponding clinical records were then reviewed to evaluate the endophthalmitis clinical features and treatment outcomes. Results: In the 12 patients identified, clinical settings included postcataract surgery (n = 4), postpenetrating keratoplasty (n = 3), endogenous source (n = 2), post-pars plana vitrectomy (n = 1), trabeculectomy bleb-associated setting (n = 1), and glaucoma drainage implant-associated setting (n = 1). All patients presented with hypopyon. Presenting visual acuity was hand motions or worse in all cases. All isolates were susceptible to ceftazidime and levofloxacin. When comparing isolates in this study with isolates from a previous study (1987 to 2001), the minimal inhibitory concentration required to inhibit 90% of isolates (MIC 90, in micrograms per milliliter) remained the same for ceftazidime (8), ciprofloxacin (0.5), imipenem (4), tobramycin (0.5), and amikacin (4). Initial treatment strategies were vitreous tap and injection (n = 9) and pars plana vitrectomy with intravitreal antibiotics (n = 3). Final visual acuity was light perception or worse in 11 of the 12 patients (92%). Five patients underwent enucleation (42%). Conclusion: All isolates were susceptible to ceftazidime and levofloxacin, and all MIC 90s for isolates in the current period compared with isolates from 1987 to 2001 remained identical. Despite early and appropriate treatment, outcomes were generally poor with a high rate of enucleation.

Endophthalmitis caused by Klebsiella species.

Purpose: To report the clinical presentation, antibiotic sensitivities, treatment strategies, and visual outcomes associated with endophthalmitis caused by Klebsiella species. Methods: A noncomparative consecutive case series. Microbiology database records were retrospectively reviewed for all patients with endophthalmitis caused by Klebsiella species from 1990 to 2012 at a large university referral center. The corresponding clinical records were then reviewed to evaluate the endophthalmitis clinical features and treatment outcomes. Results: Seven patients were identified. Clinical settings included endogenous (n = 3), posttraumatic (n = 2), trabeculectomy bleb-associated (n = 1), and postpenetrating keratoplasty (n = 1). Five patients presented with hypopyon. Presenting visual acuity ranged from 20/60 to light perception in nonendogenous cases and 1/200 to light perception in endogenous cases. Klebsiella was sensitive to aminoglycosides, third-generation cephalosporins, and second- and third-generation fluoroquinolones in all cases. Initial treatment strategies were vitreous tap and injection (n = 4), pars plana vitrectomy with intravitreal antibiotics (n = 2), and anterior chamber tap and injection (n = 1). All three endogenous cases later underwent enucleation or evisceration. In nonendogenous cases, the final visual acuity was 20/70 or better in all 4 patients. Conclusion: Endophthalmitis caused by Klebsiella species is associated with poor visual outcomes. Endogenous cases had high rates of enucleation or evisceration.