PURPOSE: To compare the corneal stromal riboflavin concentration and distribution using 2 transepithelial corneal crosslinking (CXL) systems. SETTING: Absorption Systems, San Diego, California, USA. DESIGN: Experimental study. METHODS: The stromal riboflavin concentration of 2 transepithelial CXL systems was compared in rabbit eyes in vivo. The systems were the Paracel/Vibex Xtra, comprising riboflavin 0.25% solution containing TRIS and ethylenediaminetetraacetic acid and an isotonic solution of riboflavin 0.25%, (Group 1) and the CXLO system (Group 2). Manufacturers' Instructions For Use were followed. The intensity of riboflavin fluorescence by slitlamp observation 10, 15, and 20 minutes after instillation was graded on a scale of 0 to 5. The animals were humanely killed and the corneal stromal samples analyzed with liquid chromatography and mass spectrometry. RESULTS: The mean riboflavin fluorescence intensity grades in Group 1 (4 eyes) were 3.8, 4.8, and 4.8 at 10, 15, and 20 minutes, respectively. The mean grades in Group 2 (3 eyes) were 2.0, 2.3, and 2.0, respectively. The riboflavin distribution was uniform in Group 1 but not in Group 2. The mean riboflavin concentration by liquid chromatography and mass spectrometry was 27.0 μg/g stromal tissue in Group 1 and 6.7 μg/g in Group 2. A stromal riboflavin concentration theoretically adequate for CXL, 15 μg/g, was achieved in all eyes in Group 1 and no eyes in Group 2. Slitlamp grading correlated well with liquid chromatography and mass spectrometry concentration (R = 0.940). CONCLUSIONS: The system used in Group 1 produced corneal riboflavin concentrations that were theoretically adequate for effective transepithelial CXL (≥15 μg/g), while the system in Group 2 did not. Slitlamp grading successfully estimated the corneal riboflavin concentration and can be used to ensure an adequate concentration of riboflavin in the cornea for transepithelial CXL.
Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a "brain-eye-vascular triad", and several eye diseases may also be considered as brain diseases in disguise. While the brain is part of the problem, it can also be part of the solution. Neuronal networks of the brain can "amplify" residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from vision loss.
Purpose: The purpose of this study was to investigate the contribution of mast cells to early neutrophil recruitment during ocular inflammation. Methods: In a murine model of corneal injury, the epithelium and anterior stroma were removed using a handheld motor brush. Cromolyn sodium (2% in PBS) eye drops were administered topically for mast cell inhibition. In vitro, bone marrow-derived mast cells were cultured alone or with corneal tissue. The frequencies of CD45+ inflammatory cells, CD11b+Ly6G+ neutrophils, and ckit+FcεR1+ mast cells in the cornea were assessed by flow cytometry. mRNA expression of CXCL2 was evaluated by real-time PCR and protein expression by ELISA. β-Hexosaminidase assays were performed to gauge mast cell activation. Results: Neutrophil infiltration of the cornea was observed within 1 hour of injury, with neutrophil frequencies increasing over subsequent hours. Concurrent expansion of mast cell frequencies at the cornea were observed, with mast cell activation (assessed by β-hexosaminidase levels) peaking at 6 hours after injury. Evaluation of CXCL2 mRNA and protein expression levels demonstrated augmented expression by injured corneal tissue relative to naïve corneal tissue. Mast cells were observed to constitutively express CXCL2, with significantly higher expression of CXCL2 protein compared with naïve corneal tissue. Culture with harvested injured corneas further amplified CXCL2 expression by mast cells. In vivo, mast cell inhibition was observed to decrease CXCL2 expression, limit early neutrophil infiltration, and reduce inflammatory cytokine expression by the cornea. Conclusions: Our data suggest that mast cell activation after corneal injury amplifies their secretion of CXCL2 and promotes the initiation of early neutrophil recruitment.
The emergence of diabetes as a global epidemic is accompanied by the rise in diabetes‑related retinal complications. Diabetic retinopathy, if left undetected and untreated, can lead to severe visual impairment and affect an individual's productivity and quality of life. Globally, diabetic retinopathy remains one of the leading causes of visual loss in the working‑age population. Teleophthalmology for diabetic retinopathy is an innovative means of retinal evaluation that allows identification of eyes at risk for visual loss, thereby preserving vision and decreasing the overall burden to the health care system. Numerous studies worldwide have found teleophthalmology to be a reliable and cost‑efficient alternative to traditional clinical examinations. It has reduced barriers to access to specialized eye care in both rural and urban communities. In teleophthalmology applications for diabetic retinopathy, it is critical that standardized protocols in image acquisition and evaluation are used to ensure low image ungradable rates and maintain the quality of images taken. Innovative imaging technology such as ultrawide field imaging has the potential to provide significant benefit with integration into teleophthalmology programs. Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and multidisciplinary approach with partnerships across specialties and health care professionals to attain wider acceptability and allow evidence‑based eye care to reach a much broader population.
Corneal transplantation is the most prevalent form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain graft transparency. CEnC density decreases significantly after corneal transplantation even in the absence of graft rejection. To date, different strategies have been used to enhance CEnC survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC integrity during donor cornea tissue storage and protects CEnCs against oxidative stress-induced apoptosis. However, little is known about the effect of exogenous administration of VIP on corneal transplant outcomes. We found that VIP significantly accelerates endothelial wound closure and suppresses interferon-γ- and tumor necrosis factor-α-induced CEnC apoptosis in vitro in a dose-dependent manner. In addition, we found that intracameral administration of VIP to mice undergoing syngeneic corneal transplantation with endothelial injury increases CEnC density and decreases graft opacity scores. Finally, using a mouse model of allogeneic corneal transplantation, we found for the first time that treatment with VIP significantly suppresses posttransplantation CEnC loss and improves corneal allograft survival.
Purpose: To identify genetic variants conferring susceptibility to esotropia. Esotropia is the most common form of comitant strabismus, has its highest incidence in European ancestry populations, and is believed to be inherited as a complex trait. Methods: White European American discovery cohorts with nonaccommodative (826 cases and 2991 controls) or accommodative (224 cases and 749 controls) esotropia were investigated. White European Australian and United Kingdom cohorts with nonaccommodative (689 cases and 1448 controls) or accommodative (66 cases and 264 controls) esotropia were tested for replication. We performed a genome-wide case-control association study using a mixed linear additive model. Meta-analyses of discovery and replication cohorts were then conducted. Results: A significant association with nonaccommodative esotropia was discovered (odds ratio [OR] = 1.41, P = 2.84 × 10-09) and replicated (OR = 1.23, P = 0.01) at rs2244352 [T] located within intron 1 of the WRB (tryptophan rich basic protein) gene on chromosome 21 (meta-analysis OR = 1.33, P = 9.58 × 10-11). This single nucleotide polymorphism (SNP) is differentially methylated, and there is a statistically significant skew toward paternal inheritance in the discovery cohort. Meta-analysis of the accommodative discovery and replication cohorts identified an association with rs912759 [T] (OR = 0.59, P = 1.89 × 10-08), an intergenic SNP on chromosome 1p31.1. Conclusions: This is the first genome-wide association study (GWAS) to identify significant associations in esotropia and suggests a parent-of-origin effect. Additional cohorts will permit replication and extension of these findings. Future studies of rs2244352 and WRB should provide insight into pathophysiological mechanisms underlying comitant strabismus.
OBJECTIVES: Technology-enabled non-invasive diagnostic screening (TES) using smartphones and other point-of-care medical devices was evaluated in conjunction with conventional routine health screenings for the primary care screening of patients. DESIGN: Dental conditions, cardiac ECG arrhythmias, tympanic membrane disorders, blood oxygenation levels, optic nerve disorders and neurological fitness were evaluated using FDA-approved advanced smartphone powered technologies. Routine health screenings were also conducted. A novel remote web platform was developed to allow expert physicians to examine TES data and compare efficacy with routine health screenings. SETTING: The study was conducted at a primary care centre during the 2015 Kumbh Mela in Maharashtra, India. PARTICIPANTS: 494 consenting 18-90 years old adults attending the 2015 Kumbh Mela were tested. RESULTS: TES and routine health screenings identified unique clinical conditions in distinct patients. Intraoral fluorescent imaging classified 63.3% of the population with dental caries and periodontal diseases. An association between poor oral health and cardiovascular illnesses was also identified. Tympanic membrane imaging detected eardrum abnormalities in 13.0% of the population, several with a medical history of hearing difficulties. Gait and coordination issues were discovered in eight subjects and one subject had arrhythmia. Cross-correlations were observed between low oxygen saturation and low body mass index (BMI) with smokers (p=0.0087 and p=0.0122, respectively), and high BMI was associated with elevated blood pressure in middle-aged subjects. CONCLUSIONS: TES synergistically identified clinically significant abnormalities in several subjects who otherwise presented as normal in routine health screenings. Physicians validated TES findings and used routine health screening data and medical history responses for comprehensive diagnoses for at-risk patients. TES identified high prevalence of oral diseases, hypertension, obesity and ophthalmic conditions among the middle-aged and elderly Indian population, calling for public health interventions.
PURPOSE: To review the published literature on outcomes of keratolimbal allograft (KLAL) for the surgical treatment of limbal stem cell deficiency (LSCD) and corneal blindness after severe corneal chemical injury. METHODS: Literature searches were conducted in the following electronic databases: MEDLINE, EMBASE, Science Citation Index, CINAHL, LILACS and the Cochrane Library. Standard systematic review methodology was applied. The main outcome measure was the proportion of eyes with best-corrected visual acuity (BCVA) ≥20/200 at last follow-up. Other measures of allograft success were also collected. RESULTS: We identified six reports in which KLAL outcomes in the eyes after chemical injury could be distinguished. There were no randomised controlled studies. The outcomes of KLAL in 36 eyes of 33 patients were analysed. One study with seven eyes did not specify KLAL follow-up specific to chemical injury. Median postoperative follow-up for the other 29 eyes in 26 patients was 42 months (range 6.2-114 months). In the same 29 eyes, 69% (20/29) had BCVA ≥20/200 at the last follow-up examination. Eighty-nine per cent of all eyes (32/36) underwent penetrating keratoplasty simultaneous or subsequent to KLAL. CONCLUSIONS: The number of studies where outcomes of KLAL in eyes with severe corneal chemical injury could be discerned was limited, and variability was observed in outcome reporting. The quality of evidence to support the use of KLAL in LSCD in severe chemical corneal burns was low. Standardisation and longer follow-up are needed to better define evidence-based best practice when contemplating surgical intervention for blindness after corneal chemical injury. PROSPERO REGISTRATION NUMBER: CRD42017054733.
PURPOSE: To determine the incidence of and to identify characteristics predicting significant superior oblique palsy (SOP) after adjustable superior oblique suture spacer surgery for treatment of Brown syndrome. METHODS: The medical records of patients treated for unilateral Brown syndrome with adjustable suture spacers (2005-2016) were reviewed to identify possible association of age at surgery, spacer length, surgeon performing procedure, severity of Brown syndrome, preoperative hypotropia in primary position and affected side gaze, and reduction in Brown restriction on postoperative superior oblique function. "Good" postoperative superior oblique function was defined as absence of hypertropia and diplopia in primary position and no more than intermittent diplopia in downgaze comfortably fused with ≤4Δ base-down or head tilt of <10°. Presence of postoperative hypertropia in primary position with increase in downgaze met criteria for significant SOP. Postoperative Brown restriction of ≤ -2 indicated resolution of Brown syndrome. RESULTS: Median age at surgery was 59 months, interquartile range (IQR) was 32-82 months, and median spacer length was 6 mm (range, 2-7 mm) for 19 included patients. Preoperative median hypotropia was 9Δ (IQR, 0Δ-12Δ) in primary position and 18Δ (IQR, 5Δ-22Δ) in affected side gaze. Of 19 patients, 16 (84%) achieved sufficient resolution of Brown syndrome, but 6 (32%) developed significant SOP. Modest preoperative hypotropia in affected side gaze was the only predictor of significant SOP (likelihood ratio test = 7.11; P = 0.008). Logistic regression modeling enabled estimation of risk of significant SOP based on preoperative side gaze hypotropia. CONCLUSIONS: Suture spacer surgery can result in significant SOP. Risk may be predicted by magnitude of preoperative side gaze hypotropia.
Endogenous vascular endothelial growth factor (VEGF-A) can protect retinal ganglion cells (RGC) from stress-induced cell death in ocular hypertensive glaucoma. To exploit the neuroprotective function of VEGF-A for therapeutic application in ocular disorders such as glaucoma while minimizing unwanted vascular side effects, we engineered two novel VEGF variants, eVEGF-38 and eVEGF-53. These variants of the diffusible VEGF-A isoform VEGF121 are expressed as dimeric concatamers and remain tethered to the cell membrane, thus restricting the effects of the engineered VEGF to the cells expressing the protein. For comparison, we tested a Myc-tagged version of VEGF189, an isoform that binds tightly to the extracellular matrix and heparan sulfate proteoglycans at the cell surface, supporting only autocrine and localized juxtacrine signaling. In human retinal endothelial cells (hREC), expression of eVEGF-38, eVEGF-53, or VEGF189 increased VEGFR2 phosphorylation without increasing expression of pro-inflammatory markers, relative to VEGF165 protein and vector controls. AAV2-mediated transduction of eVEGF-38, eVEGF-53, or VEGF189 into primary mouse RGC promoted synaptogenesis and increased the average total length of neurites and axons per RGC by ~ 12-fold, an increase that was mediated by VEGFR2 and PI3K/AKT signaling. Expression of eVEGF-38 in primary RGC enhanced expression of genes associated with neuritogenesis, axon outgrowth, axon guidance, and cell survival. Transduction of primary RGC with any of the membrane-associated VEGF constructs increased survival both under normal culture conditions and in the presence of the cytotoxic chemicals HO (via VEGFR2/PI3K/AKT signaling) and N-methyl-D-aspartate (via reduced Ca influx). Moreover, RGC number was increased in mouse embryonic stem cell-derived retinal organoid cultures transduced with the eVEGF-53 construct. The novel, engineered VEGF variants eVEGF-38 and eVEGF-53 show promise as potential therapeutics for retinal RGC neuroprotection when delivered using a gene therapy approach.
This paper proposes a bio-inspired visual motion estimation algorithm based on motion energy, along with its compact very-large-scale integration (VLSI) architecture using low-cost embedded systems. The algorithm mimics motion perception functions of retina, V1, and MT neurons in a primate visual system. It involves operations of ternary edge extraction, spatiotemporal filtering, motion energy extraction, and velocity integration. Moreover, we propose the concept of confidence map to indicate the reliability of estimation results on each probing location. Our algorithm involves only additions and multiplications during runtime, which is suitable for low-cost hardware implementation. The proposed VLSI architecture employs multiple (frame, pixel, and operation) levels of pipeline and massively parallel processing arrays to boost the system performance. The array unit circuits are optimized to minimize hardware resource consumption. We have prototyped the proposed architecture on a low-cost field-programmable gate array platform (Zynq 7020) running at 53-MHz clock frequency. It achieved 30-frame/s real-time performance for velocity estimation on 160 × 120 probing locations. A comprehensive evaluation experiment showed that the estimated velocity by our prototype has relatively small errors (average endpoint error < 0.5 pixel and angular error < 10°) for most motion cases.
Lysyl oxidase (LOX) is an enzyme that oxidizes lysine residues in collagens and elastin. It stabilizes or remodels the extracellular matrix and basement membrane of blood vessels. Current oncology studies have revealed that LOX is upregulated in invasive cancer cells and bolstered cell movement, and LOX was observed to promote the angiogenesis and migration of endothelial cells. In the present study, angiogenesis and migration were examined in human umbilical vein endothelial cells (HUVECs). Following cell treatment with 0.1-0.4 mM β-aminoproprionitrile (BAPN), a specific inhibitor of LOX, angiogenesis was analyzed with a fibrin gel in vitro angiogenesis assay kit and migration was examined via a Boyden Chamber assay. Angiogenesis-associated gene expression was investigated with a microarray assay and confirmed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results showed that HUVEC angiogenesis substantially increased in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and phorbol 12-myristate 13-acetate (PMA). In addition, LOX inhibition blocked the angiogenesis stimulated by VEGF bFGF and PMA, and the inhibition of LOX reduced the migration of HUVECs. Furthermore, the microarray and RT-qPCR revealed that BAPN downregulated myeloid progenitor inhibitory factor 1, and western blot analysis demonstrated that BAPN decreased the phosphorylation of MAPK and Akt, suggesting that the specific inhibitor of LOX, BAPN, may serve as an alternative strategy for preventing angiogenesis.
Optomotor response/reflex (OMR) assays are emerging as a powerful and versatile tool for phenotypic study and new drug discovery for eye and brain disorders. Yet efficient OMR assessment for visual performance in mice remains a challenge. Existing OMR testing devices for mice require a lengthy procedure and may be subject to bias due to use of artificial criteria. We developed an optimized staircase protocol that utilizes mouse head pausing behavior as a novel indicator for the absence of OMR, to allow rapid and unambiguous vision assessment. It provided a highly sensitive and reliable method that can be easily implemented into automated or manual OMR systems to allow quick and unbiased assessment for visual acuity and contrast sensitivity in mice. The sensitivity and quantitative capacity of the protocol were validated using wild type mice and an inherited mouse model of retinal degeneration - mice carrying rhodopsin deficiency and exhibiting progressive loss of photoreceptors. Our OMR system with this protocol was capable of detecting progressive visual function decline that was closely correlated with the loss of photoreceptors in rhodopsin deficient mice. It provides significant advances over the existing methods in the currently available OMR devices in terms of sensitivity, accuracy and efficiency.
This paper proposes a modified Eulerian Video Magnification (EVM) algorithm and a hardware implementation of a motion magnification core for smart image sensors. Compared to the original EVM algorithm, we perform the pixel-wise temporal bandpass filtering only once rather than multiple times on all scale layers, to reduce the memory and multiplier requirement for hardware implementation. A pixel stream processing architecture with pipelined blocks is proposed for the magnification core, enabling it to readily fit common image sensing components with streaming pixel output, while achieving higher performance with lower system cost. We implemented an FPGA-based prototype that is able to process up to 90M pixels per second and magnify subtle motion. The motion magnification results are comparable to the original algorithm running on PC.
Shiga Y, Akiyama M, Nishiguchi KM, Sato K, Shimozawa N, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Yamaji T, Iwasaki M, Tsugane S, Oze I, Mikami H, Naito M, Wakai K, Yoshikawa M, Miyake M, Yamashiro K, Kashiwagi K, Iwata T, Mabuchi F, Takamoto M, Ozaki M, Kawase K, Aihara M, Araie M, Yamamoto T, Kiuchi Y, Nakamura M, Ikeda Y, Sonoda K-H, Ishibashi T, Nitta K, Iwase A, Shirato S, Oka Y, Satoh M, Sasaki M, Fuse N, Suzuki Y, Cheng C-Y, Khor CC, Baskaran M, Perera S, Aung T, Vithana EN, Cooke Bailey JN, Kang JH, Pasquale LR, Haines JL, Wiggs JL, Burdon KP, Gharahkhani P, Hewitt AW, Mackey DA, Macgregor S, Craig JE, Allingham RR, Hauser M, Ashaye A, Budenz DL, Akafo S, Williams SEI, Kamatani Y, Nakazawa T, Kubo M. Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma. Hum Mol Genet 2018;27(8):1486-1496.Abstract
Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.
A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.
Purpose: To report a surgical approach combining scleral patch graft and tenonplasty for successful management of refractory Pseudomonas scleritis following pterygium removal with mitomycin C application. Case Report: A 75-year-old diabetic woman with a history of prior pterygium excision and mitomycin C application developed infectious necrotizing scleritis caused by . Owing to progression of scleritis despite medical management, the patient underwent surgery. Intraoperatively, extensive scleral ischemia was noted. Therefore, debridement of the necrotic tissue, scleral graft, tenonplasty to bring blood vessels to the ischemic sclera, and amniotic membrane transplantation were performed. Postoperatively, no signs of ischemia or recurrence of infection were observed. During 6 months of follow-up, the patient achieved complete restoration of the globe integrity with a non-inflamed ocular surface. Conclusion: Through restoration of blood supply to the ischemic sclera, tenonplasty is an effective adjunctive procedure in addition to conventional scleral patch graft for the treatment of refractory Pseudomonas scleritis associated with ischemia.
Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted ( < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.
PURPOSE: To evaluate the standards of harm reporting for glaucoma surgical trials and to develop a classification system for reporting surgical complication severity. DESIGN: Systematic review and Delphi consensus method. METHODS: Systematic review of glaucoma surgical trials published from January 2010 until July 2017 with a quality assessment against the CONSORT checklist for harm. A Delphi method was employed to generate consensus grading (interquartile range ≤ 2) among international glaucoma experts (n = 43) on severity of glaucoma surgical complications, and specifically for trabeculectomy and aqueous shunt complications, from 1 (no clinical significance) to 10 (most severe complication). RESULTS: Forty-seven studies were eligible. The items of the CONSORT checklist for harm that were most frequently missing were use of a validated instrument to report severity (0%), withdrawals due to harm, and subgroup analyses, both reported in 3 publications (6.4%). Most glaucoma experts participating in the Delphi process (80%) completed the second round, and consensus was achieved for all but 1 complication. The least severe complications (graded 2) were "transient loss of vision," "early low intraocular pressure," "choroidal detachment anterior to equator," "small layered hyphema < 1 mm," and "increased lens opacity not clinically significant." The most severe complications (graded 10) were "endophthalmitis" and "permanent severe loss of vision (hand movements or worse)." CONCLUSIONS: Glaucoma surgical randomized controlled trials report frequency of complications, but their severity is rarely reported. The quality of harm reporting is poor. We propose the use of a newly developed system of classification for assessing the severity of surgical complications based on consensus.