Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Coagulase-negative staphylococcal endophthalmitis: clinical severity and outcomes based on speciation.

OBJECTIVE: To identify characteristics and visual outcomes of coagulase-negative staphylococcal (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study. DESIGN: Single-centre retrospective analysis. PARTICIPANTS: Forty-two samples from 40 patients with documented CoNS endophthalmitis. METHODS: Visual acuity outcomes of CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (i.e., pars plana vitrectomy [PPV] versus vitreous tap and injection of intravitreal antibiotics [T&I]) on 42 samples from 40 patients. RESULTS: Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present. CONCLUSIONS: Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding may be a supplement to the complements the management standards set forth by the Endophthalmitis Vitrectomy Study.

Screening for Ocular Candidiasis Among Patients With Candidemia: Is It Time to Change Practice?

Ocular candidiasis (OC) complicates approximately 10% of candidemia and carries potentially severe morbidity. There are conflicting recommendations about the need for routine funduscopic examinations of candidemic patients. Indirect funduscopy is accurate and safe in diagnosing OC, and positive findings change recommended treatment. However, conclusive evidence that treatment changes improve outcomes is lacking. Bringing perspectives as infectious diseases physicians and ophthalmologists, we review controversies about OC and endorse routine screening during candidemia. We acknowledge difficulties in obtaining inpatient ophthalmologic consults and recommend studies to evaluate digital fundus photography and teleophthalmology as an alternative to funduscopic examinations by ophthalmologists in asymptomatic patients.

Hidden in the Eyes-Recurrence of Systemic Hemopathies Reportedly "In Remission": Six Cases and Review of Literature.

Background and Objectives: Secondary ocular localizations of hematological malignancies are blinding conditions with a poor prognosis, and often result in a delay in the diagnosis. Materials and Methods: We describe a series of rare cases of ocular involvement in six patients with hematological malignancies, reportedly in remission, who presented secondary ocular localizations, challenging to diagnose. Two patients had an acute lymphoblastic leukemia (ALL) and developed either a posterior scleritis or a pseudo-panuveitis with ciliary process infiltration. One patient had iris plasmacytoma and developed an anterior uveitis as a secondary presentation. Two patients had a current systemic diffuse large B-cell lymphoma (DLBCL) and were referred either for intermediate uveitis or for papilledema and vitritis with secondary retinitis. Finally, one patient with an acute myeloid leukemia (AML) presented a conjunctival localization of a myeloid sarcoma. We herein summarize the current knowledge of ophthalmologic manifestations of extramedullary hematopathies. Results: Inflammatory signs were associated with symptomatic infiltrative lesions well displayed in either the iris, the retina, the choroid, or the cavernous sinus, from the admission of the patients in the ophthalmological department. These findings suggest that patients with ALL, AML, systemic DLBCL, and myeloma can present with ophthalmic involvement, even after having been reported as in remission following an effective systemic treatment and/or allograft. Conclusions: Early detection of hidden recurrence in the eyes may permit effective treatment. Furthermore, oncologists and ophthalmologists should be aware of those rare ocular malignant locations when monitoring patient's progression after initial treatment, and close ophthalmologic examinations should be recommended when detecting patient's ocular symptoms after treatment.

Review of the Current Literature and Our Experience on the Value of OCT-angiography in White Dot Syndromes.

PURPOSE: To describe the application of OCT-A in various posterior uveitis disorders in our experience and to compare it with the available literature. METHODS: Eighteen eyes with the diagnoses of multifocal choroiditis (MFC), multifocal placoid pigment epitheliopathy (APMPPE), multiple evanescent white dot syndrome (MEWDS), tuberculous serpiginous-like choroiditis (SLC), serpiginous choroiditis (SC), and birdshot chorioretinopathy (BSCR) were studied. RESULTS: We found flow void of the choriocapillaris in patients with APMPPE, SC, MFC, BSCR, and in SLC. In contrast, perfusion of the choriocapillaris seemed normal in patients with MEWDS. CONCLUSIONS: We confirmed that OCT-A contributes new information on the physiopathology of white dot syndromes and inflammatory chorioretinopathies, notably on whether or not the choriocapillaris is involved. Comparing the OCT-A features allowed us to suggest that both APMPPE and SLC might be part of the same spectrum of inflammatory disease with primary involvement at the level of the choriocapillaris and secondary RPE damage.

Multimodal Imaging of Torpedo Maculopathy With Fluorescence Adaptive Optics Imaging of Individual Retinal Pigmented Epithelial Cells.

Torpedo maculopathy (TM) is a rare congenital defect of the retinal pigment epithelium (RPE). The RPE is often evaluated clinically using fundus autofluorescence (AF), a technique that visualizes RPE structure at the tissue level from the intrinsic AF of RPE fluorophores. TM lesions typically emit little or no AF, but this macroscopic assessment is unable to resolve the RPE cells, leaving the organization of the RPE cell mosaic in TM unknown. We used fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to show here for the first time the microscopic cellular-level structural alterations to the RPE cell mosaic in TM that underlie the tissue-level changes seen in conventional clinical imaging. We evaluated two patients with TM using conventional clinical imaging techniques and adaptive optics (AO) infrared autofluorescence (IRAF) in AOSLO. Confocal AOSLO revealed relatively normal cones outside the TM lesion but altered cone appearance within it and along its margins in both patients. We quantified cone topography and RPE cell morphometry from the fovea to the margin of the lesion in case 1 and found cone density to be within the normal range across the locations imaged. However, RPE morphometric analysis revealed disrupted RPE cells outside the margin of the lesion; the mean RPE cell area was greater than two standard deviations above the normative range up to approximately 1.5 mm from the lesion margin. Similar morphometric changes were seen to individual RPE cells in case 2. Multi-modal imaging with AOSLO reveals that RPE cells are abnormal in TM well beyond the margins of the characteristic TM lesion boundary defined with conventional clinical imaging. Since the TM fovea appears to be fully formed, with normal cone packing, it is possible that the congenital RPE defect in TM occurs relatively late in retinal development. This work demonstrates how cellular level imaging of the RPE can provide new insight into RPE pathologies, particularly for rare conditions such as TM.

The Antibacterial Comparison of 5% and 2.5% Povidone Iodine to 0.01% Hypochlorous Acid Using Corneoscleral Tissue as a Solid-Phase Medium.

PURPOSE: Prophylactic topical antiseptics used to eliminate bacteria on the ocular surface prior to ocular surgery should be both effective and non-irritating. Five percent povidone iodine (PI) is an accepted antiseptic used for prophylaxis. Dilute 2.5% PI and 0.01% hypochlorous acid (HOCl) may be more patient comfortable and equally effective. PI at 5% and 2.5% were compared to HOCl against a battery of bacterial endophthalmitis isolates using corneoscleral tissue as a solid-phase medium to determine antiseptic efficacy. METHODS: Bacteria from 20 cases of endophthalmitis were tested for the elimination of growth against topical 5% PI, 2.5% PI, HOCl, and no antiseptic using donor corneoscleral tissue. The tissue was inoculated with 103 colony forming units of bacteria prior to a 3-minute contact time with the antiseptics, placed in liquid growth medium, and monitored for growth at three days. No growth indicated antiseptic treatment success. Differences were analyzed using Chi square (χ2). RESULTS: For 20 isolates, 5% PI was comparable to 2.5% PI for preventing bacteria growth (p=0.71), and both were more effective than HOCl (p=0.004). Estimated weighted comparison over a 27-year period indicated that for all bacterial groups, except Streptococcus viridans, 5% PI was equally effective to 2.5% PI for preventing bacterial growth (p=1.0). For Streptococcus viridans, 5% PI was more effective than 2.5% PI (p=0.0001). Both concentrations of PI were more effective than HOCl (p=0.00001). CONCLUSION: Five percent PI appears to be optimal as a prophylaxis prior to ocular surgery.

ACUTE RETINAL NECROSIS: Difference in Outcome by Viral Type and Options for Antiviral Therapy.

PURPOSE: To investigate differences in outcomes of acute retinal necrosis with confirmed viral polymerase chain reaction between viral types and highlight different treatment options. METHODS: The study evaluated 22 eyes in 18 patients of polymerase chain reaction-positive acute retinal necrosis at the University of Pittsburgh Medical Center from 2007 to 2018. Outcome measures included final visual acuity, treatment paradigms, and retinal detachment rate. RESULTS: Eight eyes were polymerase chain reaction-positive for varicella zoster virus, two eyes for herpes simplex virus Type 1 (HSV-1), and 12 eyes for herpes simplex virus Type 2 (HSV-2). Final Snellen best-corrected visual acuity averaged 20/51 for varicella zoster virus, 20/25 for HSV-1, and 20/814 for HSV-2. Retinal detachment occurred in 2 (25%) of varicella zoster virus eyes and 8 (75%) of HSV-2 eyes. One eye with HSV-1 and three eyes with HSV-2 received cidofovir for treatment of refractory retinitis. CONCLUSION: Acute retinal necrosis secondary to HSV-2 tended to have persistent active retinitis with a higher rate of retinal detachment despite similar treatment protocols, suggesting that in some cases combination intravenous acyclovir and adjuvant intravitreal foscarnet injections are not sufficient. Despite the risk of renal toxicity, intravenous cidofovir may be a consideration in select patients.

Endogenous Endophthalmitis: Recommendation for Empiric Dual Antibacterial and Antifungal Therapy.

Purpose: This work compares clinical presentation and course of bacterial and fungal causes of endogenous endophthalmitis (EE). Methods: A single-institutional study of consecutive patients diagnosed with EE was conducted at the University of Pittsburgh Medical Center between September 2015 and September 2018. Exclusion criteria included history of ocular trauma, intraocular surgery or injection 6 months before presentation, or primary external ocular infection. Data included demographics, medical and ocular history, clinical examination, culture data, therapeutic interventions, final corrected visual acuity (VA), and mortality. Results: Thirty-six eyes of 26 patients were diagnosed with EE during a 3-year period. Median age at diagnosis was 55.5 years (range, 19-86 years). Based on ocular and systemic cultures, 19 patients had bacterial EE and 6 patients had fungal EE; findings from all cultures remained negative in 1 patient. All patients had risk factors for EE. Presenting VA, subjective symptom report, and objective measures of intraocular inflammation were similar between bacterial and fungal causes. Overall, EE presented indolently and was initially misdiagnosed in 19% of cases. Complications including final VA less than 20/200, retinal detachment, enucleation, or death within 6 months of diagnosis were equivalent between bacterial and fungal cases. Conclusions: The presentation of EE is remarkably different from that of exogenous endophthalmitis. Without a high index of suspicion, the indolent presentation of EE may lead to misdiagnosis. No clinical features reliably differentiated bacterial and fungal sources. This highlights the importance of considering empiric therapy for antibacterial and antifungal coverage on initial presentation.

Bilateral acute retinal necrosis caused by two separate viral etiologies.

PURPOSE: To describe an unusual case of bilateral acute retinal necrosis (ARN) that was caused by varicella zoster virus in one eye and Epstein-Barr virus in the fellow eye. OBSERVATIONS: A 67-year-old immunocompromised man presented with ARN in the left eye following a dermatomal vesicular rash, with an aqueous sample positive for varicella zoster virus. Four months later, the patient presented with panuveitis and serous retinal detachment in the right eye, with vitreous sample positive for Epstein-Barr virus and negative for varicella zoster, herpes simplex, and cytomegalovirus. CONCLUSIONS AND IMPORTANCE: We report a rare case of bilateral ARN with independent infection of each eye by different viruses; varicella zoster in the left eye and, four months later, Epstein-Barr virus in the right eye. Immunocompromised patients are vulnerable to ARN from any of its inciting viral causes, and intraocular fluid should be obtained for diagnostic confirmation from the second eye in cases of bilateral ARN.

RELATIVE QUIESCENCE OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION AFTER RESOLUTION OF POSTINJECTION ENDOPHTHALMITIS.

PURPOSE: To evaluate alterations in treatment burden and course of exudative age-related macular degeneration in patients who contracted endophthalmitis from intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. METHODS: Retrospective study at the University of Pittsburgh Medical Center examining frequency of anti-VEGF injections, activity of choroidal neovascularization, and visual acuity before and after endophthalmitis treatment. RESULTS: Twenty-one patients meeting inclusion criteria were identified, of whom 7 (33%) patients did not restart anti-VEGF treatment 12 months after endophthalmitis because of quiescence of exudative age-related macular degeneration without significant visual acuity loss (P > 0.05). Patients who resumed anti-VEGF treatment exhibited 32% and 38% decreases in injection frequency by 12 and 24 months after endophthalmitis, respectively (P < 0.05). On first optical coherence tomography follow-up, 10 patients exhibited quiescence of choroidal neovascularization activity, although there were no measurable changes in macular thickness (P > 0.05). No differences in post-endophthalmitis exudative age-related macular degeneration progression or treatment burden were observed when factoring adjuvant intravitreal steroid therapy, culture results, nor choroidal neovascularization subtypes. CONCLUSION: Endophthalmitis resolution is associated with a decrease in choroidal neovascularization activity and a reduction of anti-VEGF treatment burden in patients with exudative age-related macular degeneration.

Scleral Fixation of Intraocular Lenses with Gore-Tex Suture: Refractive Outcomes and Comparison of Lens Power Formulas.

PURPOSE: To report refractive outcomes of scleral-fixated intraocular lens (IOL) implantation with Gore-Tex (W.L. Gore & Associates, Newark, DE) suture and combined pars plana vitrectomy and compare predicted refractive outcomes among 5 IOL power calculation formulas. DESIGN: Retrospective case series. PARTICIPANTS: Patients undergoing scleral-fixated IOL implantation with Gore-Tex suture at our institution between January 2015 and June 2018. METHODS: Comparison of preoperative biometrics with postoperative refraction and calculation of predicted refractive outcome with 5 different IOL formulas. MAIN OUTCOME MEASURES: Prediction error and absolute error to compare postoperative refraction with refraction predicted by lens power calculation formulas. RESULTS: Thirty-one eyes of 31 patients were included. All power calculations assumed in-the-bag position of the IOL. The Akreos A060 (Bausch & Lomb, Rochester, NY) was implanted in 23 eyes and the CZ70BD (Alcon, Fort Worth, TX) in 8 eyes, and all lenses were sutured 3 mm behind the limbus. Average postoperative spherical equivalent (SE) was -0.79±0.95 diopters (D). Average prediction error (postoperative SE refraction minus target refraction) was -0.19±0.72 D. Postoperative SE was within 1.0 D of target in 25 of 31 patients (81%) and 2.0 D of target in 31 of 31 patients (100%). The repeated-measures analysis of variance of absolute error by lens power formula was significant (P = 0.012), with Haigis demonstrating greater error. There was no significant difference among Barrett II, Sanders-Retzlaff-Kraff theoretical (SRK/T), Holladay 2, or Hoffer Q. CONCLUSIONS: For eyes undergoing pars plana vitrectomy with scleral-sutured IOL implantation, assumption of in-the-bag IOL position when calculating lens power leads to acceptable refractive outcomes. Barrett II, SRK/T, Holladay 2, and Hoffer Q formulas were noninferior to each other.

Spontaneous closure of a chronic full thickness macular hole after failed surgery.

PURPOSE: To describe an unusual case of spontaneous closure of a chronic, large, idiopathic, stage 4 macular hole after failed surgery. OBSERVATIONS: A 75-year-old female presented with a history of a chronic, full thickness macular hole after failed surgery in the right eye. Two years after onset, she developed a fibrotic scar, which closed the macular hole and unexpectedly improved her vision. At her 4 year follow up exam, optical coherence tomography demonstrated a stable, closed macular hole with continued improvement in her visual acuity despite lack of surgical and medical intervention. CONCLUSIONS AND IMPORTANCE: The spontaneous closure of an idiopathic full thickness macular hole is an unusual event. When it occurs, it is typically in an acute setting and is attributed to bridging retinal tissue, vitreofoveal separation, and a small diameter size. In this report, we show that a chronic, large break, that failed prior surgical intervention, can spontaneously close. The formation of an underlying fibrotic scar from type 1 neovascularization bridged the macular hole and improved her visual acuity.

Pneumatic Retinopexy for Rhegmatogenous Retinal Detachment in Pseudophakia.

PURPOSE: To identify the characteristics predictive of unfavorable outcomes for pneumatic retinopexy (PR) in the repair of pseudophakic rhegmatogenous retinal detachments (RD). METHODS: A retrospective chart review was performed at a single institution to identify patients who underwent PR in pseudophakic eyes. Pre- and postoperative data were reviewed and analyzed to evaluate predictive factors of failure. RESULTS: Forty-four patients met the study criteria. PR was successful in 23 (52.3%) patients. The failed cases underwent scleral buckles, vitrectomies, or both. A retinal tear located outside the superior four clock hours was a significant predictor of PR failure. At six months post-intervention, the failure and success groups were statistically similar for vision and rate of reattachment. CONCLUSIONS: Modified criteria for PR in pseudophakia may include cases with retinal breaks within the superior four clock hours. If further surgery is required, the final vision and anatomic reattachment are not disadvantaged by the initial PR procedure.

Characteristics and Outcomes of Open Globe Trauma in the Urban versus Rural Population: A Single Center Retrospective Review.

PURPOSE: To examine the characteristics and outcomes of open globe injuries sustained by the urban population compared to the rural population. METHODS: This is a retrospective chart review of 429 patients presenting to University of Pittsburgh Medical Center (UPMC) Presbyterian Hospital with traumatic open globes from July 2005 to July 2013. RESULTS: Rural patients had a longer time which elapsed from injury to presentation (P = 0.023, average 12.04 hours vs 7.53 hours). There was a higher incidence of patient transfer prior to arrival to UPMC Presbyterian Hospital (P = 0.018), patient follow-up elsewhere (P = 0.049), and patients sustaining intraocular foreign bodies (IOFBs) (P = 0.009). CONCLUSIONS: Health care access is a well-known problem in rural areas and using rural-urban commuting area (RUCA) codes can help identify a population for risk factors or potential disparities in care. Rural patients sustained a higher rate of IOFBs; this should heighten the clinicians' suspicion during the evaluation of an open globe in other rural populations.

The Susceptibility of Bacterial Endophthalmitis Isolates to Vancomycin, Ceftazidime, and Amikacin: a 23 Year-Review.

PURPOSE: To investigate the in vitro susceptibility of Gram-positive and Gram-negative endophthalmitis bacterial isolates to vancomycin, amikacin, and ceftazidime over a 23-year period. DESIGN: Retrospective non-comparative laboratory case series. SUBJECTS: Endophthalmitis patients that were culture positive for bacteria. METHODS: Laboratory records of bacteria isolated from endophthalmitis specimens collected from January 1st 1993 to December 31st 2015 were reviewed for incidence and standard susceptibility testing. MAIN OUTCOME MEASURES: The in vitro susceptibilities of bacteria cultured from endophthalmitis to vancomycin (VAN), amikacin (AMK), and ceftazidime (CEF). RESULTS: Patients with endophthalmitis were culture positive for bacteria in 665 cases.. Coagulase negative Staphylococci (CoNS) were the most common bacteria (54.6%), followed by Streptococci (Strep) species (20.8%), Staphylococcus aureus (SA) (10.2%), other Gram-positive (other-GP) bacteria (7.4%) and Gram-negative (GN) bacteria (7.1%). All Gram-positive organisms were susceptible to VAN, with the exception of 2 isolates. The in vitro susceptibilities of bacteria to AMK were: CoNS (95.3%), SA (75.0%), Strep (8.0%), GN (95.7%), and other-GP (81.1%). The in vitro susceptibilities of bacteria to CEF were: CoNS (58.5%), SA (54.4%), Strep (84.1%), GN (93.6.%), and other-GP (52.8%). There was no difference between AMK (95.7%) and CEF (93.6%) for GN coverage. AMK provided better coverage than CEF for CoNS, SA, and other-GP bacteria respectively (p<0.05, Fisher's exact), however, CEF appeared to provide better coverage (p<0.001, Fisher's exact) for Strep than AMK. CONCLUSIONS: Based on standard in vitro susceptibility testing, vancomycin remains an optimal antibiotic choice for the treatment of Gram-positive endophthalmitis. AMK and CEF appear to provide equal GN coverage, but AMK appears to provide better coverage for CoNS, SA, and other-GP, but not Strep.