Characterization of Errors in Retinopathy of Prematurity Diagnosis by Ophthalmologists-in-Training in Middle-Income Countries.

PURPOSE: To characterize common errors in the diagnosis of retinopathy of prematurity (ROP) among ophthalmologistsin-training in middle-income countries. METHODS: In this prospective cohort study, 200 ophthalmologists-in-training from programs in Brazil, Mexico, and the Philippines participated. A secure web-based educational system was developed using a repository of more than 2,500 unique image sets of ROP, and a reference standard diagnosis was established by combining the clinical diagnosis and the image-based diagnosis by multiple experts. Twenty web-based cases of wide-field retinal images were presented, and ophthalmologists-in-training were asked to diagnose plus disease, zone, stage, and category for each eye. Trainees' responses were compared to the consensus reference standard diagnosis. Main outcome measures were frequency and types of diagnostic errors were analyzed. RESULTS: The error rate in the diagnosis of any category of ROP was between 48% and 59% for all countries. The error rate in identifying type 2 or pre-plus disease was 77%, with a tendency for overdiagnosis (27% underdiagnosis vs 50% overdiagnosis; mean difference: 23.4; 95% CI: 12.1 to 34.7; P = .005). Misdiagnosis of treatment-requiring ROP as type 2 ROP was most commonly associated with incorrectly identifying plus disease (plus disease error rate = 18% with correct category diagnosis vs 69% when misdiagnosed; mean difference: 51.0; 95% CI: 49.3 to 52.7; P = .003). CONCLUSIONS: Ophthalmologists-in-training from middle-income countries misdiagnosed ROP more than half of the time. Identification of plus disease was the salient factor leading to incorrect diagnosis. These findings emphasize the need for improved access to ROP education to improve competency in diagnosis among ophthalmologists-in-training in middle-income countries. [J Pediatr Ophthalmol Strabismus. 2023;60(5):344-352.].

Fundus autofluorescence in premature infants.

To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman's correlation against age. Additionally, patients were divided by age into group 1 (< 40 weeks of corrected gestational age (WCGA)) and group 2 (> 40 WCGA). Differences between groups were tested with the Mann-Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman's correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann-Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at < 40 WCGA (8.0 [P = 0.016] and 7.5 [P = 0.03], respectively). Patterns of FAF are described for the first time in premature infants. FAF increases gradually with age and centrifugally from the posterior pole towards the equator in premature infants.

Versatility of use of fibrin glue in wound closure and vitreo-retinal surgery.

BACKGROUND: Fibrin glue is an absorbable blood-derived product, a biological tissue adhesive which imitates the final stages of the coagulation cascade, it produces a firm clot, forming a seal along the whole length of the wound, the resultant fibrin clot degrades physiologically into granulation tissue 2 weeks after the application. Biological glue has been used extensively in many forms of surgical procedures. Its use in eye surgery has grown lately as we have evidence that showed it was effective in securing conjunctival grafts in pterygium surgery, in securing wounds after glaucoma surgery and more importantly in 20G and 23G vitrectomy. PURPOSE: The aim of this study is to present our experience in the use of fibrin glue in vitreoretinal surgery. MATERIAL AND METHODS: We included 281 eyes of 221 patients who underwent vitreoretinal surgery during the period of May 2009 to July 2012, the preoperative diagnoses were as following: proliferative diabetic retinopathy, rhegmatogenous retinal detachment, macular hole, epiretinal membrane, luxation of cataratous nucleous and cortex, intraocular lens luxation, penetrating trauma, silicone extraction, phaco + IOL + vitrectomy + Ahmed valve implant, vitreous biopsy and optic nerve pit associated to macular detachment. The procedures were performed with Alcon Accurus Surgical System 20-gauge, 23-gauge or a combination of both. We used fibrin glue in all of the 20-gauge sclerotomies and leaking 23-gauge sclerotomies, scleral wound for IOL extraction, conjunctival peritomy for buckle implantation, conjunctiva in Ahmed valve implant, corneal graft in corneal perforation in trauma and leaking corneal wounds for phacoemulsification, in an optic pit, and in subretinal space in a giant retinal tear. RESULTS: We did not use any suture in any of the patients throughout the different procedures, there was no leakage in any wounds in the postoperative period, we found no inflammatory reaction, infection, and whenever we had excess amount, it was trimmed. Two patients presented a small dehiscence of the wound that was corrected in-office with a small amount of fibrin glue in the post-operative period. CONCLUSIONS: Fibrin glue reduces surgical time, it is a good sealant, safe, with minimal allergic or toxic reactions and inflammation, minimizes bleeding, easy to undo and that eventually degrades. This small series shows that fibrin glue is a viable alternative for tissue coaptation in vitreoretinal surgery. However, further studies are required before fibrin glue takes the place of sutures.

Ophthalmic manifestations associated with SARS-CoV-2 in newborn infants: a preliminary report.

COVID-19, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), affects people of all ages. The virus can cause multiple systemic infections, principally in the respiratory tract, as well as microvascular damage. Ocular manifestations of COVID-19 are uncommon in adults and children. We describe ophthalmic manifestations in newborns detected by slit-lamp examination, fundus examination, and fluorescein angiography. All patients showed edema and hemorrhagic conjunctivitis; fundus examinations revealed cotton wool spots and vitreous hemorrhage, and microvascular damage manifested as patchy choroidal filling, peripapillary hyperfluorescence, delayed retinal filling and venous laminar flow, and boxcarring on fluorescein angiography.

A proposal of an algorithm for the diagnosis and treatment of recurrence or treatment failure of retinopathy of prematurity after anti-VEGF therapy based on a large case series.

PURPOSE: To provide a diagnostic algorithm of recurrence and treatment failure after intravitreal bevacizumab (IVB) injection for retinopathy of prematurity type 1 (ROP1) and the stepwise therapeutic approach for both conditions. METHODS: Retrospective chart review of all patients diagnosed with ROP1 initially treated with IVB in 6 tertiary referral centers of Toluca and Mexico City from 2005 to 2017. Treatment failure was defined as persistence or progression of neovascularization, elevation of the ridge, worsening of plus disease, or retinal crunch within the first week after treatment. Recurrence was defined as the new appearance of plus disease, an elevated ridge, or pathological new vessels after an initial regression of ROP following treatment. Therapy was observation, switch of anti-VEGF agent, retinal photocoagulation, vitrectomy, or a combination of two or more, depending on the severity of findings. RESULTS: A total of 672 patients who received intravitreal bevacizumab injection for ROP1 treatment were included. Of these, 2.5% (17 patients) failed to treatment, 6.8% (46 patients) developed a recurrence for ROP, and 5.5% (37 patients) carried a misdiagnosis of recurrence and were diagnosed with other than ROP1 after examination. Based on the severity of findings, patients with recurrence or treatment failure were further treated by observation, repeat anti-VEGF intravitreal injection (bevacizumab or other), laser photocoagulation, vitrectomy, or a combination of these. Based on the treatment results, a therapeutic algorithm was created. CONCLUSIONS: Intravitreal injection of anti-VEGFs for the treatment of ROP warrants close follow-up as some of these patients may have treatment failure or recurrence of the disease. It is crucial to differentiate between them to avoid a misdiagnosis and offer the correct treatment. We propose a novel algorithm for the follow-up and treatment approach of ROP1 following initial treatment with IVB. This algorithm offers a summary of our recommendations based on a large case series of ROP1 patients. It is meant to grow and expand as more clinical evidence becomes available.

Retinopathy of prematurity: incidence report of outliers based on international screening guidelines.

AIM: The objective of this study is to report the incidence of retinopathy of prematurity (ROP) outliers that fall outside the screening guidelines of the American Academy of Ophthalmology (AAO) in our country. METHODS: A retrospective review of 503 records of newborns evaluated in our institution between January 2011 and March 2017. We analyzed the data by subgroups based on gestational age (GA), birth weight (BW) and stage, focusing on the outliers that don't meet the criteria of the screening AAO guidelines (GA ≤ 30 weeks, BW ≤ 1500 g). RESULTS: Of the 503 records, 352 had some degree of ROP, 91.76% being bilateral, and 26.2% require treatment. The mean GA at delivery was 30.56 ± 2.33 weeks, and the mean BW was 1287.90 ± 338.52 g. For the current AAO/AAP ROP screening, 19.9% were outliers, of which (57%) had ROP diagnosis and (38%) required treatment. CONCLUSIONS: ROP diagnosis in newborns of BW > 1500 g or GA > 30 weeks is not uncommon in Mexico, and it is important to take this into account to adjust the selection criteria on each population to reach all the infants at risk.

Peripheral Vascular Abnormalities Seen by Ultra-Widefield Fluorescein Angiography in Adults With History of Prematurity: Report of Three Cases.

Retinopathy of prematurity (ROP) may lead to late-developing complications due to the abnormal vitreoretinal interface. In this case report, three adult patients (ages 39 years, 62 years, and 64 years) with a history of prematurity underwent imaging with ultra-widefield fluorescein angiography (UWFFA). The UWFFA demonstrated late peripheral vascular hyperfluorescence in all three patients, perivascular leakage in two of the patients, hyperfluorescent foveal avascular zone in two of the patients, peripheral avascular retina in two of the patients, vasoproliferative tumor in one of the patients, peripheral neovascularization in one of the patients, and vascular anastomosis in one of the patients. Descriptive analysis of the images is reported. The authors concluded UWFFA reveals details in adults with history of ROP that may gain importance during the follow-up or in the surgical management of these patients; however, prospective studies are needed. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:278-283.].

Influence of Computer-Generated Mosaic Photographs on Retinopathy of Prematurity Diagnosis and Management.

IMPORTANCE: Telemedicine is becoming an increasingly important component of clinical care for retinopathy of prematurity (ROP), but little information exists regarding the role of mosaic photography for ROP telemedicine diagnosis. OBJECTIVE: To examine the potential effect of computer-generated mosaic photographs on the diagnosis and management of ROP. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study performed from July 12, 2011, through September 21, 2015, images were acquired from ROP screening at 8 academic institutions, and ROP experts interpreted 40 sets (20 sets with individual fundus photographs with ≥3 fields and 20 computer-generated mosaic photographs) of wide-angle retinal images from infants with ROP. All experts independently reviewed the 40 sets and provided a diagnosis and management plan for each set presented. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the sensitivity and specificity of the ROP diagnosis by experts that was calculated using a consensus reference standard diagnosis, determined from the diagnosis of fundus photographs by 3 experienced readers in combination with the clinical diagnosis based on ophthalmoscopic examination. Mean unweighted κ statistics were used to analyze the mean intergrader agreement among experts for diagnosis of zone, stage, plus disease, and category. RESULTS: Nine ROP experts (4 women and 5 men) who have been practicing ophthalmology for a mean of 10.8 years (range, 3-24 years) consented to participate. Diagnosis by the mosaic photographs compared with diagnosis by multiple individual photographs resulted in improvements in sensitivity for diagnosis of stage 2 disease or worse (95.9% vs 88.9%; difference, 7.0; 95% CI, 3.5 to 10.5; P = .02), plus disease (85.7% vs 63.5%; difference, 22.2; 95% CI, 7.6 to 36.9; P = .02), and treatment-requiring ROP (84.4% vs 68.5%; difference, 15.9; 95% CI, 0.8 to 31.7; P = .047). With use of the κ statistic, mosaic photographs, compared with multiple individual photographs, resulted in improvements in intergrader agreement for diagnosis of plus disease or not (0.54 vs 0.40; mean κ difference, 0.14; 95% CI, 0.07 to 0.21; P = .004), stage 3 disease or worse or not (0.60 vs 0.52; mean κ difference, 0.06; 95% CI, -0.06 to 0.18; P = .04), and type 2 ROP or not (0.58 vs 0.51; mean κ difference, 0.07; 95% CI, 0.03 to 0.11; P = .04). After viewing the mosaic photographs, experts altered their choice of management in 42 of 180 responses (23.3%; 95% CI, 17.1%-29.5%). CONCLUSIONS AND RELEVANCE: Compared with multiple individual photographs, computer-generated mosaic photographs were associated with improved accuracy of image-based diagnosis for certain categories (eg, plus disease, stage 2 disease or worse, and treatment-requiring ROP) of ROP by experts. It is unclear, however, whether these findings are generalizable, and the results of this study may not be relevant to mosaic grading of other retinal vascular conditions.

New insights in diagnosis and treatment for Retinopathy of Prematurity.

The purpose of this study was to review current perspectives on diagnosis and treatment of Retinopathy of Prematurity (ROP). We performed a systematic review of how much has been produced in research published online and on print regarding ROP in different settings around the world. Early Treatment for ROP (ETROP) classification is the currently accepted classification of ROP. Fluorescein angiography and spectral domain optical coherence tomography (SD-OCT) may eventually lead to changes in the definition of ROP, and as a consequence, they will serve as a guide for treatment. Intravitreal anti-VEGF therapy has proven to be more effective in terms of lowering recurrence, allowing growth of the peripheral retina, and diminishing the incidence of retinal detachment when proliferative ROP is diagnosed. Whether anti-VEGF plus laser are better than any of these therapies separately remains a subject of discussion. Telemedicine is evolving everyday to allow access to remote areas that do not count with a retina specialist for treatment. A management algorithm is proposed according to our reference center experience. ROP is an evolving subject, with a vulnerable population of study that, once treated with good results, leads to a reduction in visual disability and in consequence, in a lifetime improvement.

Implementation and evaluation of a tele-education system for the diagnosis of ophthalmic disease by international trainees.

Tele-education systems are increasingly being utilized in medical education worldwide. Due to limited human resources in healthcare in low and middle-income countries, developing online systems that are accessible to medical trainees in underserved areas potentially represents a highly efficient and effective method of improving the quantity and quality of the health care workforce. We developed, implemented, and evaluated an interactive web-based tele-education system (based on internationally accepted, image-based guidelines) for the diagnosis of retinopathy of prematurity among ophthalmologists-in-training in Brazil, Mexico, and the Philippines. We demonstrate that participation in this tele-education program improved diagnostic accuracy and reliability, and was preferred to standard pedagogical methods. This system may be employed not only in training, but also in international certification programs, and the process may be generalizable to other image-based specialties, such as dermatology and radiology.

Comparison of iridocorneal angle in infants with retinopathy of prematurity and healthy infants using spectral domain optical coherence tomography.

PURPOSE: To compare measurements and morphologic characteristics of the iridocorneal angle in preterm infants with retinopathy of prematurity (ROP) and healthy infants using spectral domain optical coherence tomography (SD-OCT). METHODS: In this observational, case-control study, the eyes of children with ROP and healthy controls under 1 year old were imaged using SD-OCT without sedation to capture the iridocorneal angle. The ROP staging was made by a pediatric retinal specialist. The following measurements were analyzed with custom software: angle opening distance (AOD500) at 500 µm; angle opening in degrees (AOG); and angle recess area (ARA750). RESULTS: A total of 27 eyes of 14 children with ROP and 21 of 13 children without ROP were included. The mean gestational age of children in the ROP group was 30 weeks; of the controls, 35 weeks. The mean birth weight in the ROP group was 1,545 g; in the non-ROP group 2,100 g. Mean age at the time of the study was 18.1 (ROP group) vs 25.7 weeks (non-ROP). In the ROP group AOD500 was 477 µm (95% CI, 358-597 µm), AOG was 37.3° (95% CI, 30.4°-44.3°), and ARA750 was 231 mm(2) (CI 95%, 171-291 mm(2)). The same parameters on the non-ROP group were 400 µm (CI 95% 333-468 µm), 34.7° (CI 95% 30.4°-39°), and 203 mm(2) (95% CI, 171-236 mm(2)). The iris showed a more convex pattern on eyes with ROP (56% vs 23%). CONCLUSIONS: In this study cohort, children with ROP showed higher AOD500, AOG, and ARA750, perhaps because of different patterns of physiological development in children with ROP.

Optic disc and macula detection in fundus images by means of template matching.

Various methods for detecting optic disc and macula in fundus images have been developed. Our aim is to propose a fairly easy method for detecting both features jointly. This is achieved by first correcting in homogenous luminosity using a polynomial approximation of the background of the images. Secondly, the use of the cross-correlation in the frequency domain between the images and a steerable template which contains both structures. The 38 photographs used in this work belong to a local database of patients suffering diabetic retinopathy along its four severity stages. Our results showed 100% optic disc centers located within the OD area and 90% macula centers located within the MC area.

Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up.

PURPOSE: To evaluate ocular function and systemic development in premature infants treated with intravitreal bevacizumab injections for retinopathy of prematurity over a period of 5 years. METHODS: A prospective, interventional, noncomparative case study. The primary outcome measure was visual acuity. The secondary outcomes were structural assessment, other ocular functional measurements, and developmental state. RESULTS: Eighteen eyes of 13 consecutive patients were divided into 3 groups: Group 1, Stage 4 unresponsive to previous conventional treatment (n = 4); Group 2, in which conventional treatment was difficult or impossible because of inadequate visualization of the retina (n = 5); and Group 3, newly diagnosed high-risk prethreshold or threshold retinopathy of prematurity (n = 9). All patients showed initial regression of neovascularization. One patient was diagnosed with recurrence of neovascularization and was treated with intravitreal bevacizumab. Visual acuity was preserved, and median vision was 20/25 (excluding 2 operated eyes). Twelve eyes developed mainly low myopia over the years, with an overall mean value of 3.2 diopters. Electroretinograph was normal in 4 eyes that had no previous detachment. One patient showed delay in growth and neurodevelopment, whereas all the others were within the normal range. CONCLUSION: Five years of follow-up in a small series suggest that intravitreal bevacizumab for retinopathy of prematurity results in apparently preserved ocular function and systemic development.

Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the Pan-American Collaborative Retina Study Group (PACORES).

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in many diseases of the posterior pole that are characterized by macular edema and/or intraocular neovascularization. Recently anti-VEGF agents such as ranibizumab and pegaptanib sodium have been shown to be beneficial in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). However in most parts of the world, both pegaptanib sodium and ranibizumab are not readily available. Bevacizumab, a humanized recombinant monoclonal IgG antibody that binds and inhibits all VEGF isoforms, has been proposed as an alternative treatment option. METHODS: A total of 1,265 consecutive patients were injected with bevacizumab for diseases such as proliferative diabetic retinopathy, diabetic macular edema, retinal vein occlusions, and CNV of several etiologies including ARMD at eight Latin American institutions from 1 September 2005 to 31 January 2006. Of these 1,265, 92 were excluded because they were injected once and lost to follow-up. The remaining 1,173 patients constitute the subjects of this retrospective, multicenter, open label, uncontrolled interventional case series that reports the cumulative systemic and ocular adverse events following intravitreal bevacizumab during 12 months of follow-up. Patients were examined at baseline and then monthly. If the patients were unable to attend the 12-month visit, a telephone interview was conducted to assess for possible systemic complications. RESULTS: A total of 4,303 intravitreal injections of bevacizumab on 1,310 eyes was reported. All 1,173 patients were accounted for at the 12-month visit. Systemic adverse events were reported in 18 (1.5%) patients. These included seven (0.59%) cases of an acute elevation of systemic blood pressure, six (0.5%) cerebrovascular accidents, five (0.4%) myocardial infarctions, two (0.17%) iliac artery aneurysms, two (0.17%) toe amputations and five (0.4%) deaths. Ocular complications included seven (0.16%) bacterial endophthalmitis, seven (0.16%) tractional retinal detachments, four (0.09%) uveitis, and a case (0.02%) each of rhegmatogenous retinal detachment and vitreous hemorrhage. CONCLUSION: Despite the limited follow-up, repeated intravitreal injections of either 1.25 mg or 2.5 mg of bevacizumab appears to be safe and well tolerated during the 1st year.

Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity.

PURPOSE: To evaluate the role of antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity (ROP). METHODS: In this noncomparative, prospective, interventional case series, bevacizumab was injected into the vitreous of patients with ROP in three different groups: group I, patients with stage IVa or IVb ROP who had no response to conventional treatment; group II, patients with threshold ROP who were difficult to treat with conventional therapy because of poor visualization of the retina; and group III, patients with high-risk prethreshold or threshold ROP. RESULTS: Thirteen patients (18 eyes; mean age +/- SD, 4 +/- 3 months; mean follow-up, 6 months) were included in the study. We found neovascular regression in 17 eyes. One patient with stage IVa ROP had spontaneous retinal reattachment after an intravitreal injection of bevacizumab. There were no serious ocular or systemic adverse events. CONCLUSION: The use of bevacizumab may be promising in the treatment of patients with ROP. Further studies need to be performed to determine the safety and long-term efficacy of intravitreal injection of bevacizumab, either as first-line therapy or after failure of conventional therapy.

Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story.

This retrospective report describes our 20 months'experience using intravitreal injections of bevacizumab for the treatment of several retinal diseases. We describe our experience after 1765 intravitreal injections of bevacizumab in the treatment of different proliferative retinopathies - retinopathy of prematurity, choroidal neovascularization, diabetic retinopathy, among others. We believe that the findings reported in this study move us closer to a better treatment for different pathologies. However, further studies need to be performed in order to determine the safety and long-term efficacy of intravitreal bevacizumab either as first line therapy, after failure of conventional therapy, or in combination with conventional therapy.