Application and validation of a novel inflammatory score in the clinical grading of infectious endophthalmitis: The endophthalmitis management study - Report 2.

Purpose: This study was conducted to describe and validate a novel inflammatory score (IS) system in the management of infectious endophthalmitis. Methods: This was a prospective comparative non-interventional observational study. The study included the patients with clinical signs and symptoms of acute post-cataract surgery endophthalmitis (surgery within 6 weeks) with visual acuity from 6/18 to light perception. IS was scored by the clinical picture at two-levels of four ocular tissues on a scale of 0 (normal) to 4 (severe). Four masked graders of different levels of experience evaluated slit-lamp photographs. The concordance correlation coefficient was assessed between the slit-lamp clinical grading and photographic grading. We measured the concordance correlation coefficient, Pearson's correlation (indicating precision), and the bias correction factor (indicating the accuracy). Results: The study included 43 eyes of 43 patients. The concordance correlation coefficient was 0.99 (95% CI 0.995 to 0.998). Both Pearson's correlation coefficient and the bias correction were 0.99. The interclass correlation coefficient (ICC) was measured. The intra-rater ICC was 0.833 with good agreement (95% CI, 0.711 to 0.906; P < 0.001). Inter-rater ICC for consistency was 0.92 (95% CI 0.87 to 0.95). Inter-rater ICC for absolute agreement was 0.86 (95% CI 0.66 to 0.93). Conclusion: Currently used IS scoring in the study is a reliable, reproducible, and easy-to-apply scale to measure inflammation severity in endophthalmitis. We propose that it can have applications in decision-making for primary treatment and monitoring progression in acute infectious endophthalmitis.

Brilliant Blue G toxicity in macular hole surgeries: A report on combined phototoxicity and dye-induced macular damage.

PURPOSE: Vitrectomy with brilliant blue G (BBG) assisted internal limiting membrane (ILM) peeling is the standard operational technique in macular hole surgeries. However, BBG dye, though considered safe and nontoxic, can also occasionally lead to macular toxicity. This study aims to describe the clinical features and characteristics of four eyes who developed macular toxicity after following surgery for macular hole repair. METHODS: Retrospective review of four consecutive cases of macular toxicity after conventional BBG assisted ILM peeling. All the cases reviewed, their operative surgical notes were retrieved and analyzed. The ILM was stained twice during surgery with prolonged intraoperative surgical time. RESULTS: All four cases had a prolonged surgical time and the ILM was stained twice during surgery in all cases. The area of macular toxicity was corresponding to the area of ILM peeling which had been exposed to repeated staining by BBG dye. By the end of one month, all four cases had foveal thinning along with choriocapillary atrophy. The mean BCVA was 20/80 before surgery and the final mean visual acuity was <20/800. CONCLUSION: This report highlights the occurrence of macular and choriocapillary atrophy due to prolonged focal endoillumination and the increased risk of toxicity with repeated dye staining.

A retrospective analysis of ultra-widefield photograph (Optos) documentation of retinopathy of prematurity at a tertiary eye care outpatient setup: the Indian Twin Cities ROP Study, report number 11.

PURPOSE: To demonstrate the usefulness of ultrawide-field fundus (UWF) photography for documentation in retinopathy of prematurity (ROP). METHODS: The medical records of infants with ROP who underwent at least one sitting of UWF fundus photography in addition to binocular indirect ophthalmoscopy (BIO) from April 2018 to September 2020 were analyzed retrospectively. BIO was conducted by a trained ROP specialist, and final diagnosis and treatment were based solely on BIO findings. All fundus photographs were captured on Optos UWF camera (Dunfermline, UK) in a flying baby position. Demographic details and fundus findings on BIO and fundus photographs were analyzed. RESULTS: Of the 187 infants who met inclusion criteria for successful imaging, 22 (11.7%) had findings that were discordant with BIO. Although no posterior disease was missed, 4 infants who received treatment would not have been treated based solely on UWF photography findings. Of the 60 babies whose images did not meet the inclusion criteria for successful imaging, 41 had ROP that required intervention. CONCLUSIONS: In our patient cohort, UWF photography proved useful in documenting the initial and follow-up findings of preterm babies with ROP.

Endophthalmitis management study. Report #1. Protocol.

To date, the Endophthalmitis Vitrectomy Study (EVS) has remained the hallmark of evidence-based management of acute bacterial endophthalmitis after cataract surgery with an intraocular lens. In the last quarter-century since its publication, several studies have reported that the microbiological spectrum of endophthalmitis is not the same across the world; there is emerging antibiotic resistance of gram-negative microorganisms to the EVS recommended antibiotics; there are newer molecules that could cross the blood-retinal barrier; the advances in vitreous surgery have become safer than before, and there are newer methods of microbiological evaluation. One of the often-mentioned drawbacks of the EVS was not recruiting grossly infected eyes with poor visibility of the iris and vitreous. Keeping these factors in mind, a new prospective multi-centered randomized study, the Endophthalmitis Management Study (EMS), is designed. The EMS will recruit all post-cataract surgery endophthalmitis patients irrespective of severity (including suspected fungal infection); the EMS will use quantifiable inflammatory score instead of the presenting vision to allocate for surgery, randomize the eyes to two different combinations of intravitreal antibiotics and use the newer microbiological diagnostic techniques. We believe the EMS findings will complement the EVS recommendations.

Optical coherence tomography angiography findings of fellow eye of proliferative macular telangiectasia type 2: Long term study.

PURPOSE: To report the characteristics of non-proliferative fellow eyes in patients with unilateral proliferative macular telangiectasia type 2 (MacTel). METHODS: This was a multicenter, retrospective study and included fellow eyes of eyes with subretinal neovascular membrane (SRNVM). Multimodal imaging including fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA) was performed. OCT and OCTA measurements included central macular thickness (CMT), subfoveal choroidal thickness (SFCT), foveal avascular zone (FAZ) area and qualitative parameters such as distortion or enlargement of FAZ, increased inter-vascular spacing, dilated, tortuous vessel at margin of FAZ, crowding of vessel, and loss of choriocapillaris (CC). RESULTS: Thirteen fellow eyes of 13 patients with mean age of 63.6 ± 12.0 years were included. Fellow eyes had various stages of the diseases - stage 2 (four eyes), 3 (six eyes), and 4 (three eyes). OCTA showed increased intervascular spacing (8; 61.5%), dilated (11; 84.6%), and elongated vessels (8; 61.5%) at the margin of the FAZ, crowding of vessels (6; 46.2%), capillary non-perfusion areas outside the FAZ (4; 30.8%), and areas of CC loss (4; 30.8%). Mean follow-up was 9.1 ± 12.9 months. Out of six eyes with follow-up of ⩾12 months, two developed SRNVM at 18 and 33 months with OCTA showing crowding and entanglement of dilated retinal vessels in deep capillary plexus at baseline which corresponded to the area affected by SRNVM. CONCLUSION: Fellow eyes of proliferative MacTel showed established disease stages on OCTA with progressive capillary crowding and entanglement of vessels likely corresponding to the future site of SRNVM.

Posterior microphthalmos with pigmentary retinopathy.

We report a case of 19-year-old man with gradual diminution of vision in both eyes since childhood. His best-corrected visual acuity was 20/160, N16 in the right eye and 20/200, N16 in the left eye. Slit-lamp biomicroscopic examination revealed normal cornea, anterior segment, intraocular pressure and lens. Fundus of both eyes showed crowded optic disc with pigmentary changes. Ancillary tests were performed to aid in the diagnosis. A-scan ultrasound revealed short axial lengths with normal corneal diameter, anterior chamber depth and lens thickness. Optical coherence tomography of both eyes showed inner retinal layer folds. Electroretinogram of both eyes showed extinguished photopic as well as scoptopic responses. A diagnosis of posterior microphthalmos with pigmentary retinopathy was made. The patient was counselled regarding nature of the disease and the condition was managed with low vision aids.

Syphilitic chorioretinitis presenting as a choroidal granuloma.

A rare case of syphilitic uveitis presenting as a choroidal granuloma is described in this case report. The clinical picture resembled that of a tubercular choroidal granuloma. However, the patient was positive for treponemal (treponema pallidum hemagglutination assay) as well as non-treponemal tests (venereal disease research laboratory test) for syphilis. Therefore, the patient was treated for ocular syphilis and responded to antisyphilitic therapy. There was a complete resolution of the lesion at the end of 14 days of treatment.

Clinical Presentations and Comparative Outcomes of Delayed-Onset Low-Grade Endophthalmitis Managed with or Without Intraocular Lens Explantation.

PURPOSE: To compare the outcomes of delayed-onset low-grade endophthalmitis managed with and without intraocular lens (IOL) explantation. SETTING: Tertiary eye-care research institute in southern India. DESIGN: Retrospective comparative case series. METHODS: The study included all cases of post-cataract surgery delayed-onset endophthalmitis from January 1990 to January 2019. Time to endophthalmitis, duration of symptoms, presenting visual acuity, time to IOL explantation when performed, resolution after explantation, number of intravitreal injections, and final visual acuity were compared in the IOL non-explanted and IOL explanted groups. RESULTS: There were 115 eyes - 61 eyes in the IOL non-explant and 54 eyes in the IOL explant group. Between the two groups there was no statistically significant difference in age (58.37 ± 14.05 and 56.04 ± 14.96 years, respectively; p=0.35), vision at presentation (>20/400 in 29.5% and 29.6% eyes, respectively; p=0.98), and the duration of follow-up (14.38 ± 16.05, median 8.5 months and 7.06 ± 3.55, median 6 months respectively; p=0.43). There was a statistically significant difference between the IOL non-explant and IOL-explant groups in the time to resolution of inflammation (92.70 ± 36.28 and 45.33±11.2 days, respectively; p <0.0001) and the number of intravitreal injections (4.57 ± 0.75, median 5 and 2.79±2.11, median 2 respectively, p=0.005). Persistent/recurrent inflammation at 6 months was recorded in 18.03% and 5.55% in the IOL non-explant and IOL explant eyes, respectively (p=0.04). Favorable functional outcome was seen in 50.81% vs 68.51% in IOL non-explant and explant eyes, respectively (p=0.05). CONCLUSION: IOL explantation in delayed-onset endophthalmitis helps in earlier resolution of inflammation, need for lesser number of intravitreal injections and a trend towards better functional outcomes.

Two-year outcomes of intravitreal ziv-aflibercept.

AIM: To assess the two-year outcome of intravitreal ziv-aflibercept (IVZ) in eyes with macular diseases. METHODS: Consecutive subjects with various macular diseases that received six or more of 0.05 mL IVZ (1.25 mg) injections with at least 1 year follow-up were included. Outcome measures were best-corrected visual acuity (BCVA) (logarithm of the minimum angle of resolution) and central macular thickness (CMT) on spectral domain optical coherence tomography. Paired comparison was done using Wilcoxon signed-rank test calculator. RESULTS: 107 eyes of 91 subjects received IVZ and were followed with mean±SD follow-up interval of 1.48±0.44 months following treat and extend or pro-re-nata protocol. The distribution included neovascular macular degeneration (42 eyes), diabetic macular oedema (32 eyes) and macular oedema secondary to retinal vein occlusion (11 eyes). Fifty eyes were naive, while 57 eyes were previously treated. Combining all disease categories, CMT decreased significantly by 133.0±153.0 µm at the 24-month follow-up (P<0.001) with BCVA gain of 0.35±0.37 at the 24-month follow-up (P<0.001) with mean number of injections of 8.5 at month 12, 2.4 between 12 and 18 month and 1.7 between 18 and 24 month. Ocular and systemic adverse effects included one episode of transient uveitis and one instance of central retinal artery occlusion after 1121 injections. CONCLUSIONS: IVZ appears safe and efficacious in the therapy of macular diseases through 2 years.

Intravitreal Ziv-Aflibercept: Clinical Effects and Economic Impact.

During the past decade, drugs that inhibit the actions of vascular endothelial growth factor (VEGF) have become standard-of-care treatment for a variety of chorioretinal vascular conditions. The off-label, intravitreal use of ziv-aflibercept (Zaltrap) has provided clinicians with an additional cost-effective drug. The commercial preparation of ziv-aflibercept contains the same aflibercept (VEGF-trap) molecule as Eylea but has a much higher osmolarity (1000 mOsm/kg vs 300 mOsm/kg). Initial concerns regarding cytotoxicity and long-term safety of intravitreal ziv-aflibercept have been largely negated after a series of publications failed to identify adverse ocular and systemic side effects. Both treatment-naive and anti-VEGF‒resistant cases of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and choroidal neovascular membrane (CNVM) may respond as well to ziv-aflibercept as to aflibercept. A higher dose of ziv-aflibercept (2 mg in 0.08 mL) does not cause any adverse effects during short-term follow-up period (1 month). Data from various sources suggest that ziv-aflibercept may be as cost effective as bevacizumab, thereby making it an attractive treatment option in low- and middle-income countries. However, problems with off-label use, compounding, and counterfeiting limit its availability in many countries. Data from prospective, randomized, multicenter clinical trials are still required to convince physicians and regulatory bodies of its clinical efficacy and potential as early therapy.