Pan-viral Antibody Repertoire of Aqueous Humor in Cytomegalovirus Uveitis.

PURPOSE: The identification of infectious etiologies is important in the management of uveitis. Ocular fluid testing is required but multiplex testing faces challenges due to limited volume sampled. The determination of antibody repertoire of aqueous humor (AH) is not possible with conventional assays. We hence investigated the use of a highly multiplexable serological assay VirScan, a Phage ImmunoPrecipitation Sequencing (PhIP-Seq) library derived from the sequences of over 200 viruses, to determine the antibody composition of AH in uveitis patients. DESIGN: Prospective case control study METHODS: We analyzed the paired AH and plasma samples of 11 immunocompetent patients with active PCR-positive CMV anterior uveitis, and the AH of 34 control cataract surgery patients with no known uveitis in an institutional practice. The samples were tested using VirScan PhIP-Seq and the entire pan-viral antibody repertoire was determined using peptide tile ranking by normalized counts to identify significant antibodies enrichment against all viruses with human tropism. RESULTS: Significant enrichment of antibodies to Herpesviridae, Picornavirdae and Paramyxoviridae were detectable in 20 microliters of AH samples from CMV uveitis patients and controls. CMV uveitis patients had relative enrichment of anti-CMV antibodies in AH compared to their plasma. Epitope-level mapping identified significant enrichment of antibodies against CMV tegument protein pp150 (p=1.5e-06) and envelope glycoprotein B (p=0.0045) in the AH compared to controls. CONCLUSIONS: Our proof-of-concept study not only shed light on the antibody repertoire of AH but expands the utility of PhIP-Seq to future studies to detect antibodies in AH in the study of inflammatory eye diseases.

Femtosecond laser-assisted cataract surgery for complex cataracts - A review.

Since its inception in 2009, femtosecond laser-assisted cataract surgery (FLACS) has become an alternative to conventional phacoemulsification cataract surgery (CPCS). Clinical studies were unable to demonstrate superior visual outcomes, but revealed reduced endothelial cell loss. More recently, the cost-effectiveness of FLACS over CPCS in routine cataract surgeries has been challenged. However, the unique abilities of FLACS to customize anterior capsulotomies precisely, soften and fragment the nucleus without capsular bag stress, and create corneal incisions may have special utility in complex cataract and less-common scenarios. In this article, we review the unique role of FLACS in complex cataract surgeries and how it could play a role to improve the safety and predictability of nonroutine cataract surgery.

Demyelinating plaque-associated uveitis.

PURPOSE: To report the clinical and fluorescein angiographic (FA) features of demyelinating plaque-associated uveitis (DPU), a subset of uveitis in which patients have demyelinating plaques on the brain/cervical magnetic resonance image (MRI) but do not meet the criteria for multiple sclerosis (MS). METHODS: In this retrospective observational study, Persian Patients were diagnosed with DPU and included if (1) they never satisfied the MS criteria, (2) all other possible etiologies were excluded, and (3) they were followed for at least 2 years. RESULTS: After a median follow-up of 3 years (interquartile range, 2.0-5.3), 8 out of 40 (20%) patients diagnosed with DPU were excluded as they subsequently met the MS criteria. Of remaining 32 patients studied, the mean age was 36.3±9.9 (range 20-56 years), and 30 (93.8%) were female. Twenty-four (75.0%) showed bilateral involvement and 27 (84.4%) had insidious-chronic course. Uveitis was classified as intermediate (with or without anterior uveitis) in 29 (90.6%) and isolated anterior in 3 (9.4%) patients. Nine (28.1%) patients had at least one systemic neurological complaint. Ocular findings were: granulomatous keratic precipitates in 43/44 (97.7%) eyes; snowballs in 25/52 (48.1%) eyes; snowbanks in 4/52 (7.7%) eyes; cystoid macular edema in 20/56 (35.7%) eyes; and optic neuritis in 5/56 (8.9%) eyes. Visual acuity was ≥ 20/40 in 39 eyes (69.6%) at presentation which improved to 46 eyes (81.2%) at 2-year follow up. The two most frequent findings in FA were optic disc leakage/staining in 44/52 (81.5%) eyes, and peripheral retinal perivascular leakage in 39/52 (76.9%) eyes, which in 14/52 (26.9%) eyes extended beyond the equator. CONCLUSION: DPU usually presents as a bilateral chronic granulomatous intermediate and, less often, isolated anterior uveitis, especially in females. Most are neurologically asymptomatic. Visual outcome is generally favorable. In FA, peripheral retinal perivascular leakage is common. DPU patients have an increased tendency to develop MS and should be prohibited from anti-TNF treatment.

Risk factors affecting visual outcomes following dropped nucleus after cataract surgery.

BACKGROUND/ AIMS: To describe the visual outcomes in eyes with dropped nucleus during phacoemulsification surgery. SETTING: Singapore National Eye Centre (SNEC). DESIGN: Retrospective chart review of prospectively reported cases of dropped nucleus. METHODS: The clinical charts of all cases of dropped nucleus (Jan 2001 to Dec 2016) were retrospectively reviewed for patient demographics, surgeon type, stage of surgery, timing of pars plana vitrectomy (PPV), and complications. Visual success was defined as best corrected visual acuity (BCVA) ≥ 20/40 at last review. Final risk factors affecting visual success were identified using multivariate logistic regression analysis. RESULTS: Incidence of dropped nucleus following cataract surgery was 0.17% (n = 292). Duration of follow-up was 25.5 months (mean), 18.5 months (median). There was a statistically significant difference in dropped nucleus rate between Residents (0.3%) and Faculty (0.14%) (x2 = 38.2, P < 0.001), but ensuing major complications rates were similar. PPV was performed in 251 eyes (87.2%). At final examination, 202 cases (85.2%) achieved BCVA 20/40 or better, after excluding patients with co-existing ocular pathology. Timing of vitrectomy (delayed vs same-day) did not influence the final visual success (x2 = 0.969, p = 0.51). Risk factors for poor visual outcomes included age >70 years, absence of intraocular lens (IOL) implant, and presence of major complications. CONCLUSION: Overall incidence of dropped nucleus in SNEC was 0.17%, with BCVA of 20/40 or better in 85.2% cases. Visual prognosis was influenced by patient's age, presence of IOL implant or additional major complications.

Capsular phimosis with intraocular lens tilt and decentration.

A 34-year-old woman with quiescent bilateral intermediate uveitis maintained on once-daily dexamethasone 0.1% eyedrops, complicated by left cataract and glaucoma controlled with a single antiglaucoma medication, presented for cataract surgery. Her left corrected distance visual acuity (CDVA) was 20/40 because of a posterior subcapsular lens opacity. The anterior chamber angles appeared closed in all 4 quadrants on gonioscopy. Ultrasound biomicroscopy (UBM) confirmed the gonioscopy findings and, in addition, revealed a crystalline lens thickness of 5.53 mm, normal ciliary body structure, and multiple localized chorioretinal scars with membranes over the pars plana region. She underwent left phacoemulsification, goniosynechiolysis, and in-the-bag implantation of a single-piece monofocal hydrophobic acrylic intraocular lens (IOL). On the first postoperative day, she achieved pinhole vision of 20/70 (-6 diopters [D] myopia to balance with the fellow eye). There was mild anterior chamber cellular activity and flare, consistent with postoperative inflammation. Her intraocular pressure (IOP) was 16 mm Hg without antiglaucoma therapy. She was advised to continue the prednisolone acetate 1% eyedrops 6 times daily and to reduce it to 4 times daily after a week for the next 4 weeks. At 1 month, she was refracted to 20/40 N5, and the eye was quiescent. Optical coherence tomography showed that the macular was normal. The topical steroids were gradually tapered to the preoperative level. However, a month later, she returned complaining of deteriorating vision while using twice-daily steroid eyedrops. Her CDVA was 20/60. Slitlamp examination revealed anterior capsule fibrosis and capsular phimosis, resulting in partial obstruction of the visual axis and mild decentration of the IOL superior temporally (Figure 1JOURNAL/jcrs/04.03/02158034-202310000-00013/figure1/v/2023-09-28T161738Z/r/image-tiff). The anterior segment was quiescent. The pupil could only be dilated to 4.5 mm despite the absence of posterior synechiae. Fundus examination revealed a normal-looking quiescent posterior segment. Her IOP was 16 mm Hg. UBM showed a thickened anterior capsule, intact zonular fibers, and a posteriorly bowed and decentered IOL within the capsular bag (Figure 2JOURNAL/jcrs/04.03/02158034-202310000-00013/figure2/v/2023-09-28T161738Z/r/image-tiff). She was referred for further management. Discuss how you would manage this problem, explaining your decisions. How would you be able to avoid the same problem when operating on her fellow eye?

Approach to a spontaneously ruptured posterior polar cataract.

A 61-year-old man presented with gradual blurring of vision and glare in both eyes for a couple of years, with worsening of the vision in his right eye over the past 2 months. He had no medical history of note. On clinical examination, his visual acuities were 20/80 in the right eye and 20/30 in the left eye, uncorrected. The cornea was clear, and the anterior chamber (AC) was deep in both eyes. He had bilateral mild nuclear sclerosis with round central onion-ring-like posterior opacities. The opacities measured approximately 2 mm in diameter and were marginally larger in the right eye than in the left eye (Figure 1JOURNAL/jcrs/04.03/02158034-202305000-00018/figure1/v/2023-04-20T184543Z/r/image-tiff). In addition, there were 2 curvilinear lines across the right posterior capsule (PC), one of which passed across the lens opacity (Figure 2JOURNAL/jcrs/04.03/02158034-202305000-00018/figure2/v/2023-04-20T184543Z/r/image-tiff). Fundus examination was normal in both eyes, and the vitreous was clear. Optical coherence tomography (OCT) of the macular and optic nerve in both eyes was normal. The endothelial cell count in both eyes exceeded 2000 cells/mm2. He had been told by a previous ophthalmologist to have bilateral cataracts and was now keen for surgery starting with the right eye. He works as a manager in a large company and is an avid golf player. He is emmetropic and wears spectacles for near work. Optical biometry using predicated posterior corneal astigmatism did not recommend a toric intraocular lens (IOL). He had done his internet research on IOL options and requested trifocal IOLs. What is your surgical plan for right cataract removal? Explain which IOL you would choose to implant.

Surgical decisions in the setting of zonulopathy.

An 85-year-old man with a history of type 2 diabetes, pseudoexfoliation (PXF) in both eyes, and tamsulosin use was referred for the evaluation of a dense cataract in the right eye and a subluxated intraocular lens (IOL) in the left eye. Unfortunately, his surgery in the left eye was complicated by diffuse zonulopathy. The referring surgeon placed a 3-piece IOL in the sulcus. However, the passively fixated 3-piece IOL moved inferiorly causing monocular diplopia for over a year. Because the patient was pleased with the IOL immediately postoperatively, a refixation procedure was performed in the form of sulcus placement with iris suture fixation in the left eye. Fortunately, the iris-fixated IOL in the left eye has remained well centered and stable without cystoid macular edema (CME) or chronic inflammation for over 8 months. The patient is on no ocular medications and has no family history of glaucoma. He now needs cataract surgery in the right eye and is extremely apprehensive because of his difficult course in the left eye. The corrected distance visual acuity is 20/70 in the right eye and 20/25 in the left eye. Intraocular pressures (IOPs) measure 20 mm Hg in the right eye and 14 mm Hg in the left eye by Goldmann tonometry. Pachymetry is 536 µm in the right eye and 543 µm in the left eye. Pupils are round with minimal reactivity and without a relative afferent pupillary defect. Extraocular motility is normal in both eyes, and confrontation visual fields is full in both eyes. Gonioscopy reveals an angle open to the pigmented trabecular meshwork (PTM) in the right eye and the ciliary body in the left eye with 1+ PTM and without peripheral anterior synechia in both eyes. The retinal nerve fiber layer and macular optical coherence tomography are normal in both eyes. On slitlamp examination, pertinent findings include pseudoexfoliative changes at the pupillary margin with poor dilation of 3.5 mm in both eyes; the anterior chamber (AC) is shallow but adequate in the right eye and deep and quiet with rare pigmented cells in the left eye. There is a 5+ nuclear sclerotic cataract with pseudoexfoliative changes on the anterior capsule and no obvious phacodonesis in the right eye and a 3-piece posterior chamber IOL in the sulcus fixated to the iris with 10-0 polypropylene sutures at 6 and 12 o'clock without pseudophacodonesis in the left eye. Dilated fundus examination reveals a cup-to-disc ratio of 0.4 with healthy neuroretinal rims in both eyes, posterior vitreous detachments in both eyes, and no evidence of diabetic retinopathy in both eyes. All other findings are unremarkable. How would you counsel this patient regarding his risk factors for surgery in the right eye? What surgical maneuvers would you use to remove the cataract safely? How would you stabilize the IOL if the capsule bag becomes compromised due to zonulopathy?

Endothelial keratoplasty with anterior chamber intraocular lens versus secondary posterior chamber intraocular lens.

AIM: To describe the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with an anterior chamber intraocular lens (ACIOL) compared to secondary posterior chamber (PC) IOL. METHODS: This was a retrospective comparative cohort study. The clinical data of 82 eyes from 82 consecutive patients with pseudophakic (PBK) or aphakic bullous keratopathy (ABK) who either underwent DSAEK with retained or secondary ACIOL (n=23) or DSAEK with IOL exchange and/or secondary PCIOL (retropupillary iris-claw IOL, n=25; intrascleral-fixated IOL, n=29; or sulcus IOL, n=5) were analysed. The main outcome measures were graft survival and complications up to 5 years. RESULTS: The graft survival in the secondary PCIOL group was superior than the ACIOL group over 5 years (year 1, 100.0% vs 100.0%; year 3, 94.7% vs 75.0%; year 5, 91.1% vs 60.6%, p=0.022). The presence of an ACIOL was a significant risk factor associated with graft failure (HR, 4.801; 95% CI, 1.406 to 16.396, p=0.012) compared to a secondary PCIOL. There was no significant difference in the rate of graft detachment and elevated intraocular pressure between the groups. There were five cases (9.3%) of IOL subluxation or dislocation in the retropupillary iris-claw and intrascleral-fixated IOL groups. CONCLUSIONS: Eyes that underwent DSAEK with ACIOL in situ had poorer long-term graft survival compared with those with secondary PCIOL. Intraocular lens exchange was not associated with a higher complication rate. In ABK or PBK eyes with ACIOL, we recommend performing IOL exchange and/or secondary PCIOL implantation combined with endothelial keratoplasty.

Iris Manifestations in Inadequately Treated Chronic Recurrent Vogt-Koyanagi-Harada Disease.

PURPOSE: To describe the iris changes in chronic recurrent Vogt-Koyanagi-Harada Disease (VKH). METHODS: Retrospective case series. Clinical features of 3 VKH patients who developed bilateral depigmentation of the iris are described. RESULTS: Patients had delayed diagnosis and inadequately treated chronic recurrent VKH. Patient 1 presented with bilateral multiple contiguous small granulomatous iris stromal lesions, severe diffuse iris swelling more severe near the iris root, producing peripheral iris undulations. Diffuse iris atrophy and peripheral depigmentation subsequently developed. Patient 2 presented with peripheral iris depigmentation, atrophy of the ciliary zone iris stroma and sparing of the sphincter pupillae, giving a 'sunflower appearance.' Patient 3 had extensive iris depigmentation, atrophy, and transillumination defects involving the entire iris. CONCLUSION: Uncontrolled bilateral diffuse granulomatous stromal iris inflammation leads to subsequent depigmentation, transillumination defects and atrophy, beginning in the peripheral iris. Sphincter pupillae is initially spared but complete iris atrophy may develop.

Candida Endophthalmitis Treated Successfully With Isavuconazole: A Case Report.

Candida endophthalmitis is a serious complication of candidemia. Diagnosis requires identification of ocular lesions on dilated fundoscopy, aided by isolation of the organism from blood and/or vitreous humor. However, the initial ophthalmological examination may be negative in some cases. Experience with isavuconazole for the treatment of Candida endophthalmitis is limited. We present a case of a 65-year-old woman with metastatic breast cancer on chemotherapy who developed Candida dubliniensis endophthalmitis with initial negative ophthalmological examination. She was treated with vitrectomy and 6 weeks of oral fluconazole. Despite vitrectomy and culture-directed antifungal treatment, management was complicated by lack of response to fluconazole and intolerance to other antifungals, necessitating the use of isavuconazole, which proved efficacious.

Vitreoretinal Lymphoma.

Vitreoretinal lymphoma (VRL) is a rare variant of primary central nervous system lymphoma (PCNSL), mostly of diffuse large B cell lymphoma, which affects the retina and/or the vitreous with or without optic nerve involvement. The disease course is aggressive. Up to 90% of the patients develop central nervous system lymphoma within one year. The diagnosis of VRL is challenging due to nonspecific chronic and relapsing uveitis and is made by anterior chamber tab or vitreous aspirate biopsy. There is no established treatment protocol for VRL patients with bilateral involvement without CNS involvement. There are suggestions to use only intravitreal chemotherapy with methotrexate and/or rituximab. Alternatively, systemic high-dose MTX treatment or external beam radiotherapy is used. Further studies are needed to prove and confirm the prophylactic systemic therapy in preventing CNS involvement in limited VRL.

Management of the subluxated crystalline lens: A review.

Cataract surgery for the subluxated crystalline lens is challenging. A thorough preoperative evaluation is important to determine the appropriate surgical approach for lens removal and the subsequent technique of intraocular lens placement. Important considerations include the extent and location of zonular weakness, and whether the zonular deficiency is caused by a static or progressive disease. The capsular bag should be preserved where possible. Creating a good-sized and centred continuous curvilinear capsulorhexis is crucial to facilitate the use of capsular retractors and capsular tension devices, which provide capsular stability. Nucleus sculpting and rotation should be minimised to reduce zonular stress. Being cognisant of the possible intraoperative complications that may occur at each stage of the surgery and knowing how to reduce the risk of these complications occurring will enable surgeons to perform safe cataract surgery in these complex cases.

Consensus Recommendations for the Diagnosis of Vitreoretinal Lymphoma.

PURPOSE: To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). METHODS: Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. RESULTS: Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. CONCLUSIONS: A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.

Cytomegalovirus (CMV) causes clinical issues primarily in immune-suppressed conditions. CMV-associated anterior uveitis (CMV-AU) is a notable new disease entity manifesting recurrent ocular inflammation in immunocompetent individuals. As patient demographics indicated contributions from genetic background and immunosenescence as possible underlying pathological mechanisms, we analyzed the immunogenetics of the cohort in conjunction with cell phenotypes to identify molecular signatures of CMV-AU. Among the immune cell types, natural killer (NK) cells are main responders against CMV. Therefore, we first characterized variants of polymorphic genes that encode differences in CMV-related human NK cell responses (Killer cell Immunoglobulin-like Receptors (KIR) and HLA class I) in 122 CMV-AU patients. The cases were then stratified according to their genetic features and NK cells were analyzed for human CMV-related markers (CD57, KLRG1, NKG2C) by flow cytometry. KIR3DL1 and HLA class I combinations encoding strong receptor-ligand interactions were present at substantially higher frequencies in CMV-AU. In these cases, NK cell profiling revealed expansion of the subset co-expressing CD57 and KLRG1, and together with KIR3DL1 and the CMV-recognizing NKG2C receptor. The findings imply that a mechanism of CMV-AU pathogenesis likely involves CMV-responding NK cells co-expressing CD57/KLRG1/NKG2C that develop on a genetic background of KIR3DL1/HLA-B allotypes encoding strong receptor-ligand interactions.

Keratic Precipitates: The Underutilized Diagnostic Clue.

The morphology of keratic precipitates (KPs) may yield important diagnostic clues. However, KPs have not been described in a standardized manner and the traditional classification of granulomatous or non-granulomatous KPs is not helpful in differentiating infectious from noninfectious uveitis. A granulomatous uveitis may initially appear non-granulomatous. We suggest three ways to examine KPs that may aid in differentiating the infectious from noninfectious etiologies. The first method is the in vivo confocal microscopy (IVCM) description and classification of KPs, in which the "non-granulomatous" subset of dendritiform and infiltrative KPs should be differentiated from smooth-rounded KPs and globular KPs which are "granulomatous." The second and third clues are the distribution and color of the KPs. KPs that extend beyond the midline may suggest an infective cause, and fresh pigmented KPs suggest a viral cause. Careful examination of the KPs may immediately reveal the clues to the diagnosis, minimizing unnecessary tests and costs.

Randomized Controlled Trial Comparing Femtosecond Laser-Assisted with Conventional Phacoemulsification on Dense Cataracts.

PURPOSE: To compare the benefit of femtosecond laser-assisted cataract surgery (FLACS) versus phacoemulsification (PE) and 2 fragmentation patterns in managing dense cataracts. DESIGN: Randomized controlled trial. METHODS: Patients with nuclear opacity (NO) grade >5 (Lens Opacities Classification System III) were enrolled at the Singapore National Eye Centre. Patients who were unsuitable for FLACS, whose corneal endothelial cell count (ECC) was <1,500 cells/mm2, or had cataracts with additional complexities were excluded from the study. Eyes were randomized to PE, 600 µm grid (FLACSg), or 16-segment fragmentation (FLACS16) in 2:1:1 ratio. The Victus (Bausch & Lomb) laser platform and in situ phacoemulsification chop technique was used. Data for patient demographics, preoperative, and 1 month postoperative best-corrected visual acuity (BCVA), ECC, effective phacoemulsification time (EPT), and perioperative complications were collected. Outcome measurements were the loss of ECC at 1 month and EPT. RESULTS: Ninety-three patients were randomized to PE (48), FLACSg (22), and FLACS16 (23). Majority were Chinese (87; 93.5%). Mean age was 74.3 ± 8.8 years of age. Cataracts were mostly graded as NO 5-6 (49; 61.3%). EPT among treatment arms was not different (P = .097, one-way ANOVA) but was significantly higher for NO >6 than NO <6 (P < .001, general linear model). ECC loss was significantly less in FLACSg than in PE (P = .018, Bonferroni correction). Mean 1-month postoperative LogMAR BCVA (0.23 ± 0.20) was significantly better than preoperative BCVA (1.02 ± 0.85; P < .001, paired t test) but not different between PE and FLACS. CONCLUSIONS: FLACSg but not FLACS16 significantly lowered the mean ECC loss during phacoemulsification in dense cataracts.

Viral anterior uveitis.

Viral anterior uveitis (VAU) needs to be suspected in anterior uveitis (AU) associated with elevated intraocular pressure, corneal involvement, and iris atrophic changes. Common etiologies of VAU include herpes simplex, varicella-zoster, cytomegalovirus, and rubella virus. Clinical presentations can vary from granulomatous AU with corneal involvement, Posner-Schlossman syndrome, Fuchs uveitis syndrome, and endothelitis. Due to overlapping clinical manifestations between the different viruses, diagnostic tests like polymerase chain reaction and Goldmann-Witmer coefficient analysis on the aqueous humor may help in identifying etiology to plan and monitor treatment.

Evolving Consensus Experience of the IUSG-IOIS-FOIS with Uveitis in the Time of COVID-19 Infection.

This document summarizes the experience of the International Uveitis Study Group (IUSG), the Intraocular Inflammation Society (IOIS), and the Foster Ocular Inflammation Society (FOIS) and can aid as a guide for the treatment of uveitis patients in the era of COVID-19 pandemic.