Abstract
Purpose:
Evaluate the reliability of clinical grading of diabetic retinopathy (DR) severity compared to grading on ultra-widefield pseudocolor fundus (UWF-CF) and ultra-widefield fluorescein angiography (UWF-FA) images and their relative detection of sight-threatening DR (STDR) and referable DR.
Methods:
We analyzed 184 diabetic eyes. UWF-CF and UWF-FA images were graded based on the International Clinical Diabetic Retinopathy (ICDR) severity scale. Agreement between clinical and UWF-based severity grading was evaluated using Cohen’s kappa coefficient. The rate of STDR and referable DR was evaluated for each grading method.
Results:
We found moderate agreement between clinical grading and UWF-CF (k= .456, p <.001) and between UWF-CF and UWF-FA (k= .443, p <.001). Agreement between clinical grading and UWF-FA was fair (k=.397, p <.001). UWF-based grading identified a higher DR grade in 56 eyes (30%) on UWF-CF and 85 eyes (46.2%) on UWF-FA. Compared to clinical grading, UWF-FA detected a higher rate of STDR (44%; 81/184 vs 22.3%; 41/184), while UWF-CF detected more referable eyes (58.1%; 107/184 vs 45.65%; 84/184).
Conclusion:
UWF-CF is a valuable tool for identifying referable eyes and can be a useful, non-invasive adjunct to clinical grading. Our results suggest that UWF-FA is particularly useful for detecting unsuspected STDR in eyes with clinically referable DR.
Keywords: Diabetic Retinopathy, fluorescein angiography, imaging, retina, ultra-widefield
Summary statement:
Our study aimed to determine whether ultrawide-field (UWF) imaging offers an advantage to clinical grading of diabetic retinopathy (DR). Studying the agreement between clinical and UWF grading, we found that UWF was a helpful adjunct to clinical grading for detecting referable eyes and those with sight-threatening DR.
Introduction
Approximately one-third of all patients diagnosed with Diabetes Mellitus (DM) will develop diabetic retinopathy (DR)1, the leading cause of preventable blindness in the working adult population.2,3 Currently, the gold standard for detecting DR is a dilated fundus examination. Retinal imaging technologies have greatly helped clinicians in diagnosing, treating, and predicting the progression of DR.4 However, retinal imaging is often not part of the DR screening process, where DR severity grading often relies solely on clinical examination.
Using retinal imaging, the ETDRS (Early Treatment Diabetic Retinopathy Study) established the importance of early detection of DR and developed standardized grading scales and methods for accurate diagnosis and monitoring of diabetic patients.5,6 The ETDRS grading system describes 13 distinct levels of DR severity ranging from absence of disease to vision-threatening proliferative diabetic retinopathy (PDR). This grading is based on lesions quantified by certified graders inside the area known as the ETDRS 7 standard fields (7SF), which focus on the posterior pole of the retina.7 It should be emphasized that the ETDRS 7SF fundus photos only concentrate on lesions found in the central 75 degrees of the retina, which is a mere 30–35% of the total retina. The development of ultra-widefield (UWF) imaging has greatly improved visualization of the retina, expanding the view to nearly 82% (up to 200 degrees) of the total retina, representing an essential advancement in the field of ophthalmology.8,9.
Fluorescein angiography (FA) is still considered the best method for assessing vascular lesions, and extending the application of FA to UWF images highlighted the importance of peripheral vascular lesions.10,11,12
Previous studies focusing on the advantages of UWF imaging over the ETDRS 7SF fields suggested that visualization of predominantly peripheral lesions (PPL) on both UWF pseudo-color fundus (CF) and UWF-FA imaging lead to higher severity grading in 9 – 15% of eyes.13,14,15 Ashraf et al.16 reported that UWF-FA detects 3.5-fold higher microaneurysm load (p<0.001) than UWF-CF, especially in peripheral fields. In another study, Rocha et al.17 reported that at least 37.6% of eyes graded on UWF-CF show higher severity when graded on UWF-FA.
Although comparing different imaging techniques can help in choosing the appropriate screening method, it is still necessary to examine the differences between clinical grading and image grading. The DRCR group (Diabetic Retinopathy Clinical Research) inquired about the reliability of eyes graded solely through ophthalmoscopy compared to grading on ETDRS 7SF images and reported only moderate agreement of 75% (k=0.55).18 Other previous studies have reported substantial agreement (k= 0.73, k= 0.74, and k= 0.75) between ophthalmoscopy and grading in ETDRS 7-field stereoscopic images.19,20,21 However, all these studies were limited to the area contained by the ETDRS 7SF in the posterior pole, potentially overlooking the contribution of peripheral lesions to DR severity.
This study aims to evaluate the role of UWF imaging in DR, by exploring the agreement between it and clinical ophthalmoscopic grading of DR severity. To do this, we conducted a cross-sectional observational study across a wide range of DR severity and compared the accuracy of DR grading based on clinical ophthalmoscopy with grading on UWF-CF and UWF-FA. We were particularly interested in the role of UWF-imaging in detecting eyes that would otherwise be missed clinically despite being at high risk for complications.
Methods
This prospective observational study was conducted at Northwestern Memorial Hospital in Chicago. The Northwestern University Ethics Committee approved the study protocol in accordance with the Declaration of Helsinki for research involving human subjects. Subjects signed an informed consent before enrolling. Health Insurance Portability and Accountability Act (HIPAA) compliance was maintained.
One hundred and eight patients were enrolled between October 2021 and December 2022. Subjects were at least 18 years old and diagnosed with Diabetes Mellitus type 1 or 2. Exclusion criteria included the presence of center-involved diabetic macular edema (DME), history of intravitreal anti-vascular endothelial growth factor (VEGF) or steroid in the last six months, any ocular condition that could affect retinopathy status or visual acuity (VA), major ocular surgery in the previous three months and glycosylated hemoglobin >10%.
Patients were evaluated by ophthalmologists or optometrists, who performed dilated ophthalmoscopy to determine the severity of DR based on clinical findings. Mydriatic UWF-CF and UWF-FA photos were performed by certified photographers using an Optos California (Optos PLC, Scotland, U.K.) UWF imaging device. 5cc of fluorescein dye was injected intravenously. The images were analyzed using the Optos advance software (version v4.4.33.107911, Optos PLC, Scotland, U.K.). To simulate the area corresponding to the ETDRS 7SF, a mask template was placed over the UWF images to grade the posterior pole. This template mask was later switched for one that allowed visualization of the entirety of the image for peripheral retinal analysis while still demarcating the ETDRS 7SF (Figure 1).
Fig 1. Optos advance mask of the ETDRS 7-fields overlaid onto ultra-widefield pseudocolor fundus and fluorescein angiography images of the same eye.
A, ultra-widefield pseudocolor fundus image with overlaid contour of ETDRS 7 fields and extended fields. B, ETDRS 7-field mask in ultra-widefield pseudocolor fundus image. C, ultra-widefield fluorescein angiography image with overlaid contour of ETDRS 7-fields and extended fields. D, ETDRS 7 field mask overlaid on ultra-widefield fluorescein angiography image.
UWF-CF and UWF-FA images were graded based on the International Clinical Diabetic Retinopathy severity scale (ICDR) (details below) by two trained graders (D.C. and N.D.). Intergrader correlation was excellent for both UWF-CF and UWF-FA (ICC= 0.952, p< 0.001; ICC=0.934, p<0.001, respectively); a senior third grader (H.F.) resolved the disagreements. All graders were masked to the clinical staging of the subjects.
ICDR grading for moderate NPDR (modNPDR) is defined as “more than just microaneurysms, but less than severe NPDR (sNPDR)”, and sNPDR is defined as “>20 intra-retinal hemorrhages in each of 4 quadrants, definite venous beading (VB) in ≥2 quadrants, intra-retinal microvascular abnormalities (IRMA) in ≥1 quadrant, and no signs of PDR”.22 Given that intra-retinal hemorrhages are not visible in FA images, eyes clinically graded as mild or modNPDR with no signs of other lesions were considered “unchanged” on UWF-FA unless sNPDR criteria were met.
The presence of PPL was reported for both imaging techniques to account for their impact on severity grading. A lesion is considered predominantly peripheral when more than 50% of it is observed outside the ETDRS 7 fields.23 We also considered the impact of these grading approaches (clinical, UWF-CF, and UWF-FA) on the classification of eyes as referable DR, defined as modNPDR or higher severity4, or sight-threatening DR (STDR), defined as sNPDR or PDR.
Statistical analysis was done using Statistical Package for the Social Sciences (version 28.0.1.0, IBM SPSS Statistics, New York, U.S.A.). The agreement between clinical severity and image-based grading was evaluated with Cohen’s Kappa coefficient for nominal variables. Pearson chi-square was used to compare the percent of referable eyes between grading techniques. A p-value less than 0.05 was considered statistically significant.
Results
The analysis included 184 eyes from 108 patients with DR severity grades ranging from DM no DR to PDR. Patient demographics and clinical characteristics are shown in Table 1.
Table 1.
Patient Demographics and Clinical Characteristics
| Subject characteristic | Study population |
|---|---|
| Eyes/patients | 184 / 108 |
| Age (years), mean ± SD | 58.02 ± 14.54 |
| Gender, N (%) | |
| Male | 47 (43.5) |
| Female | 61 (56.5) |
| DM type, N (%) | |
| Type 1 | 21 (19.4) |
| Type 2 | 87 (80.6) |
| DM duration (years), mean ± SD | 19.19 ± 16.58 |
| A1c (%), mean ± SD | 7.02 ± 1.21 |
| BMI (Kg/m 2 ), mean ± SD | 32.25 ± 7.62 |
Abbreviations: DM, Diabetes Mellitus; A1c, glycosylated hemoglobin; BMI, Body Mass Index; SD, Standard Deviation.
The distribution of the DR severity based on the grading method (clinical, UWF-CF photos, and UWF-FA) is shown in Figure 2.
Fig 2. Distribution of eyes according to clinical, ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography grading.
Abbreviations: DMnoDR, diabetes mellitus without diabetic retinopathy; miNPDR, mild non-proliferative diabetic retinopathy; modNPDR, moderate non-proliferative diabetic retinopathy; sNPDR, severe non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; UWF-PCF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography.
We found moderate agreement between clinical grading and UWF-CF (k= .456, p <.001) and between UWF-CF and UWF-FA (k= .443, p <.001). Comparing clinical grading and UWF-FA showed a fair agreement (k=.397, p <.001). Overall, 56 of 184 eyes (30.4%) were deemed to have a higher DR stage on UWF-CF photos and 85 of 184 eyes (46.2%) on UWF-FA compared to clinical grading. In contrast, compared to clinical grading, only 20/184 eyes (10.87%) and 5/184 eyes (2.72%) had a lower severity grade on UWF-CF and UWF-FA. 108/184 eyes (58.7%) and 94/184 eyes (51.09%) showed no difference between clinical grade and UWF-CF and UWF-FA, respectively.
Based on UWF-CF grading, 33% of eyes clinically deemed to have DMnoDR had evidence of retinopathy, 21.62% (16/74) had miNPDR, while 12.16% (9/74) had hemorrhages or other lesions corresponding to the modNPDR stage. 16/26 eyes (61.5%) clinically graded as miNPDR were found to have referrable DR. Of these, 68.75% (11/16 eyes) had evidence of hemorrhages, and 31.25% (5/16 eyes) had at least one quadrant with IRMA and were therefore considered sNPDR. Finally, 6/70 (8.57%) eyes clinically graded as modNPDR or sNPDR had evidence of neovascularization (NV) and consequently were considered PDR. (Figure 3)
Fig 3. Grading discrepancy between clinical, ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography images.
Abbreviations: DMnoDR, diabetes mellitus without diabetic retinopathy; miNPDR, mild non-proliferative diabetic retinopathy; modNPDR, moderate non-proliferative diabetic retinopathy; sNPDR, severe non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; UWF-PCF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography.
On UWF-FA images, a higher level of DR severity was seen in 42 of 74 eyes (56.76%) clinically graded as DMnoDR. 38/143 eyes (26.5%) clinically deemed as either DMnoDR, miNPDR, or modNPDR demonstrated evidence of IRMA, elevating their grading to sNPDR. Finally, 5/69 eyes (7.5%) clinically considered as either mild or modNPDR, and 7/27 eyes (25.93%) clinically graded as sNPDR showed neovascularization and were therefore graded as PDR. (Figure 3)
We found a statistically significant difference between clinical, UWF-CF, and UWF-FA grading of referrable eyes and STDR (p<0.001). UWF-FA detected the most eyes with STDR, with 81 out of 184 (44%) eyes. UWF-CF and clinical grading detected 49 out of 184 (26.6%) eyes and 41 out of 184 (22.3%) eyes, respectively. (Figure 4)
Fig 4. Sight threatening vs. non-sight threatening diabetic retinopathy eyes based on clinical, ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography.
Abbreviations: STDR, sight threatening diabetic retinopathy; NSTDR, non-sight threatening diabetic retinopathy; UWF-PCF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography.
UWF-CF grading identified 107 out of 184 (58.1%) referable eyes, while UWF-FA and clinical ophthalmoscopy detected 96 out of 184 (52.17%) and 84 out of 184 (45.65%) referable eyes, respectively (Figure 5). This analysis also showed that 3% (5/184) of eyes without referable DR on UWF-CF showed a referable DR grade in UWF-FA. In contrast, 18.5% (34/184) of eyes deemed to have modNPDR in UWF-CF demonstrated a higher grade, either sNPDR or PDR, on UWF-FA, showing an important role for FA in eyes with these, referable levels of DR severity. Figure 6 shows two examples of eyes where clinical severity was underestimated by at least two steps. Pictures A and B show an eye clinically graded as DMnoDR, which showed a modNPDR severity in UWF-CF and an sNPDR severity in UWF-FA. Similarly, images C and D show an eye clinically deemed as miNPDR, which showed a mod NPDR severity in UWF-CF and a sNPDR severity in UWF-FA.
Fig 5. Referable vs. non-referable eyes based on clinical, ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography.
Abbreviations: STDR, sight threatening diabetic retinopathy; NSTDR, non-sight threatening diabetic retinopathy; UWF-PCF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography.
Fig 6.
A and B, eye Clinically graded as no diabetic retinopathy present showing microaneurysms and intraretinal hemorrhage in ultrawide-field pseudocolor fundus images, and intra-retinal microvascular abnormalities in ultra-widefield fluorescein angiography. Circles in A show an intraretinal hemorrhage.
C and D, eye clinically graded as mild non proliferative diabetic retinopathy that revealed intraretinal hemorrhages in ultrawide-field pseudocolor fundus images and, intraretinal microvascular abnormalities in ultrawide-field fluorescein angiography. Circles in C show intraretinal hemorrhages, arrows show microaneurysms. Circles in D show intraretinal microvascular abnormalities.
In our study population, PPL was observed in 39.1% (72/184) of all eyes on UWF-CF and 46.2% (85/184 eyes) on UWF-FA. PPL led to higher DR severity grades in 23 of 56 (41.1%) eyes on UWF-CF and 23 of 85 (27.1%) eyes in UWF-FA. In contrast, lesions in the posterior pole accounted for a higher severity grade in most eyes: 33 out of 56 eyes (58.9%) on UWF-CF and 62 out of 85 eyes (72.9%) on UWF-FA (Table 2).
Table 2.
Overview of clinical, ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography images severity grading and lesions leading to higher severity grade.
| Clinical Severity Grade | n (eyes) | UWF-CF Grade Relative to Clinical Grade (eyes) | Location of UWF-CF Lesions Leading to Higher Severity Grade (eyes) | UWF-FA Grade Relative to Clinical Grade (eyes) | Location of UWF-FA Lesions Leading to Higher Severity Grade (eyes) | ||||
|---|---|---|---|---|---|---|---|---|---|
| DM no DR | 74 | More Severe | 25 (33.8%) | PPL | 12 (48%) | More Severe | 42 (56.8%) | PPL | 19 (45.2%) |
| Posterior | 13 (52%) | Posterior | 23 (54.8%) | ||||||
| No Change | 49 (66.2%) | No Change | 32 (43.2%) | ||||||
| Mild NPDR | 26 | More Severe | 16 (61.5%) | PPL | 5 (31.3%) | More Severe | 5 (19.2%) | PPL | 2 (40%) |
| Posterior | 11 (68.8%) | Posterior | 3 (60%) | ||||||
| No Change | 7 (26.9%) | No Change | 20 (76.9%) | ||||||
| Less Severe | 3 (11.5%) | Less Severe | 1 (3.8%) | ||||||
| Moderate NPDR | 43 | More Severe | 12 (27.9%) | PPL | 5 (41.7%) | More Severe | 31 (72.1%) | PPL | 2 (6.5%) |
| Posterior | 7 (58.3%) | Posterior | 29 (93.5%) | ||||||
| No Change | 29 (67.4%) | No Change | 12 (27.9%) | ||||||
| Less Severe | 2 (4.7%) | Less Severe | 0 (0%) | ||||||
| Severe NPDR | 27 | More Severe | 3 (11.1%) | PPL | 1 (33.3%) | More Severe | 7 (25.9%) | PPL | 0 (0%) |
| Posterior | 2 (66.7%) | Posterior | 7 (100%) | ||||||
| No Change | 13 (48.1%) | No Change | 18 (66.7%) | ||||||
| Less Severe | 11 (40.7%) | Less Severe | 2 (7.4%) | ||||||
| PDR | 14 | No Change | 10 (71.4%) | No Change | 12 (85.7%) | ||||
| Less Severe | 4 (28.6%) | Less Severe | 2 (14.3%) | ||||||
Abbreviations: UWF-CF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography; NA, not applicable; PPL, predominantly peripheral lesions; DM no DR, diabetes mellitus without retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.
Table 3 shows that retina specialists were more accurate in DR grading than optometrists. Only two eyes were evaluated by a general ophthalmologist and did not show an increase in severity after UWF imaging grading. When we analyzed eyes evaluated by retina specialists separately showed moderate agreement between clinical grading and UWF-CF (k= .483, p <.001) and UWF-FA (k= .470, p <.001).
Table 3.
Diabetic retinopathy severity increase observed in ultra-widefield pseudocolor fundus and ultra-widefield fluorescein angiography according to clinician level of specialty.
| Level of specialty (n = eyes evaluated) | Severity increase of UWF-CF relative to Clinical Grade (n,%) | Severity increase of UWF-FA relative to Clinical Grade (n,%) |
|---|---|---|
| Optometrists (n, 43) | 20 (46.5%) | 31 (72%) |
| Retina Specialists (n, 139) | 36 (25.9%) | 54 (39%) |
| Ophthalmologists (n, 2) | 0 | 0 |
Abbreviations: UWF-CF, ultra-widefield pseudocolor fundus; UWF-FA, ultra-widefield fluorescein angiography
Discussion
This study analyzed the agreement between clinical and UWF-imaging for grading DR and found that a large proportion of eyes were deemed to have higher severity on UWF-CF and UWF-FA than originally assessed on clinical grading. Using UWF-FA led to the classification of 40 more eyes (21.74%, 40/184) as STDR compared to clinical grading, while UWF-CF detected 23 more referable eyes (12.5%, 23/184). Our findings highlight the difficulty of detecting retinal neovascularization and IRMA during clinical ophthalmoscopy, lesions that are more readily detected with UWF imaging, especially UWF-FA.
Wessel et al. reported that UWF-FA captures 1.9 times more neovascularization than color fundus photos restricted to the ETDRS 7 fields.12 Further, The ETDRS reports 11 and 13 emphasized the utility of FA for assessing the blood-retina barrier integrity and perfusion status.24,25 Interestingly, UWF-FA in our study detected more STDR eyes. At the same time, UWF-CF identified significantly more referable eyes than clinical examination and UWF-FA. This discrepancy may be ascribed to intra-retinal hemorrhages in modNPDR eyes that were not visible in UWF-FA. Our findings suggest that while the risks accompanying fluorescein may not justify the benefit of the observed lesions in the less severe stages of DR26, the use of UWF-CF provides a non-invasive and highly accurate option for detecting referable eyes. We suggest that UWF-FA be reserved for those eyes that show referable DR (moderate NPDR or worse) on UWF-CF or clinical grading. Referable lesions that are underestimated by clinicians may preclude these patients from receiving appropriate care, which could ultimately result in preventable vision loss.2 Figure 7 shows our suggestions for imaging during DR screening along with the AAO practice pattern follow-up recommendations according to DR severity.
Fig 7. Recommended screening using ultra-widefield imaging.
If clinical examination reveals no diabetic retinopathy (DR) or mild non-proliferative diabetic retinopathy (NPDR), proceed with color fundus (CF) images. If the clinical examination or CF reveals referable DR severity, proceed with ultra-widefield fluorescein angiography (UWF-FA). Follow-up according to the American Academy of Ophthalmology (AAO) preferred practice pattern.
* Only 5% (2/43) of eyes clinically deemed as modNPDR had lower severity on UWF-CF imaging. On the other hand, 17% (12/70) of eyes deemed to have moderate or severe NPDR on clinical exam revealed PDR severity in UWF-FA, highlighting the rationale for directing these cases directly to angiography.
Abbreviations: UWF, ultra-widefield; UWF-CF, ultra-widefield pseudocolor fundus; CF, color fundus; UWF-FA, ultra-widefield fluorescein angiography; DMnoDR, diabetes mellitus without retinopathy; miNPDR, mild non-proliferative diabetic retinopathy; modNPDR, moderate non-proliferative diabetic retinopathy; sNPDR, severe non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy.
At least 3 eyes within each clinical DR grade showed a dramatic increase by two severity grades or demonstrated PDR based on UWF imaging. IRMA and neovascularization were the most common lesions observed in UWF-FA that were missed by clinicians. At the same time, hemorrhages, IRMA, and NV were the most common clinically missed lesions observed in UWF-CF. These findings highlight the improved visualization of lesions on UWF-FA and UWF-CF, which allow a more accurate assessment of DR severity.
Posterior lesions (rather than PPL) accounted for most of the higher grades on UWF imaging, 33 out of 56 eyes (58.9%) on UWF-CF and 62 out of 85 eyes (72.9%) on UWF-FA. This finding differs in its scope from previous studies that suggested that a significant number of lesions may be present in the retinal periphery outside of the ETDRS 7 fields.27 Our study focused on lesions that changed the severity assessment, rather than lesion location in general, which was not the focus of our study. Our findings highlight the utility of retinal images to improve the assessment of lesions, posterior and peripheral, that may be overlooked by clinicians during ophthalmoscopic examination across severity stages. Since UWF imaging is not widely available, we encourage the use of standard color fundus images in conjunction with clinical examination to better assess DR severity. It is worth mentioning that while PPL evaluation does not replace the findings observed in the posterior pole, PPL has been proposed to predict worsening of NPDR and should be considered when deciding on treatment and follow-up schedule. Recent DRCR studies have shown that the presence of PPL on fluorescein angiography increases the risk of DR progression by 3.2-fold, and the development of PDR by 4.7-fold over 4 years.28 Patients who were deemed to have a significant increase in severity after UWF image grading in our study were placed on a closer observation schedule. None of these patients required immediate treatment for active PDR or center-involved DME, which were exclusion criteria for enrollment in this study. Since these patients are actively followed, any complications that arise would lead to timely management based on the revised, more stringent follow-up recommendations.
Compared to retina specialists, our results show that optometrists may underestimate grading more frequently than retina specialists. Given that optometrists tend to be the first contact for patients as they start their ophthalmic evaluations for DR, the use of UWF images in conjunction with ophthalmic evaluation may be of great benefit in that regard.
Out of the 19 eyes that decreased in severity after undergoing UWF-CF or UWF-FA grading, 11 out of 19 were clinically graded as severe or moderate, and decreased by one grade only. In 26.3% (5/19) of these eyes, clinicians could not confirm if the lesion observed clinically were IRMA or neovascularization.
This study presented some limitations. Clinicians participating in this study were not given severity grading criteria to follow during the ophthalmoscopic examination, basing their diagnosis on their professional clinical opinion. The clinical DMnoDR group was the largest in our study. This may explain why this group showed the most variance on UWF imaging grading. Further studies, including eyes with more severe DR, should be performed. Also, type 1 DM population was poorly represented in this study; given that type 1 DM patients generally present with more severe DR due to the longer duration of DM, their inclusion in further studies would generate a more varied and meaningful sample.2
Conclusion
Clinical grading tends to underestimate the severity of the disease by two grades in around 16–27% of eyes affected by DR. UWF-CF is a valuable tool for identifying referable eyes, and it can accurately stage DR without being invasive. UWF-FA is even more precise than clinical ophthalmoscopy and UWF-CF in detecting eyes with STDR, making it a useful method for identifying advanced stages of DR, when the risk of vision loss is high (STDR). Overall, UWF imaging is effective at detecting lesions in the posterior pole and retinal periphery and provides an important adjunct to clinical evaluation and management of these patients.
Funding:
This study was supported by NIH Grant R01EY31815 (AAF), Ruth L. Kirschstein National Research Service Award, Grant/Award Number: 5T32DK007169 (DCC), and a collaborative grant agreement from Boehringer Ingelheim.
Footnotes
Presented at ARVO (Association for Research in Vision and Ophthalmology) 2023 annual meeting – April 25th, 2023. New Orleans, Louisiana.
Conflicts of interest: AAF serves as consultant for Regeneron, Roche/Genentech, Boehringer Ingelheim, RegenXbio, and 3Helix.
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