- The patient presented with gradual decreased vision and significant glare. Exam found moderate NPDR with CSME in the right eye and microaneurysms and hemorrhages in the left eye. OCT showed intraretinal fluid in the right macula. - The findings were classified as moderate NPDR with CSME in the right eye. Treatment of intravitreal aflibercept was recommended for the CSME with possible focal laser. Regular screening is important given the patient's diabetes.

1. Prepared and presented by
Lori Myers, MD
PGY1 Ophthalmology Intern

2. HPI: 74 YO male with IDDM with past BDR here for “abnormal
teleretinal imaging.” His last eye exam was 2 years ago.
C/o a gradual decrease in the sharpness of his vision, both at distance
and near. C/o significant glare with night driving. He was told by his
PCP that he has cataracts. He is inquiring about surgery.
Type II DM since 1985, started insulin 2 years ago. BG “going great.”
Last Hgb A1c 8.4%. No nephropathy per PCP records.

3. POH: Mild NPDR (2012),
ocular allergies, spectacles
Ocular Meds:
 ketotifen
 ATs PRN
PMH:
 IDDM
 HTN (138/90)
 Osteoarthritis
 CAD s/p stents
Systemic Meds:
 Insulin
 Lisinopril
 Metoprolol
 Aspirin
 Clopidogrel
FamH: none-contributory
SocH: (-) Tob, (-) EtOH

4. MRx
OD -0.25 + 0.25 x 180 (20/40)
OS -0.25 + 1.25 x 142 (20/50+2)
Glare - OD 20/150, OS 20/300
Pupils – 4  2mm OU, No RAPD
CVF - Full OU
EOM - Full OU
IOP –
OD 23 mmHg
OS 20 mmHg
SLE
OU
Lids -mild MGD
Conjunctiva - quiet
Cornea - clear
AC - deep & quiet
Iris - normal, no NVI
Lens: -
1+ NS
2+ cortical spokes
2+ PSC w/ central plaque

5. On external view, taken from teleretinal imaging, you can see cortical spokes
highlighted with retroillumination. Is this the cause of the patient’s decreased vision?

6. An inexperienced ophthalmology resident might be thinking “home run, it’s
cataracts, sign them up for surgery!” But, wait…we should probably get a good
look at the retina, as the patient did have NPDR in their history.

7. Describe what you see:
Small diabetic hemorrhages and MAs in macula and around
superior and inferior arcades. Fine, frond-like, abnormal
vessles in the supero-temporal macula near the superior
arcades. Flame hemorrhage superior to the disc. Small
exudate temporal to fovea. Small BRAO inferior arcade-likely
chronic.

8. Peripheral views show a few more small hemorrhages

9. Similarly, in the left eye you can see
microaneurysms and small hemorrhages in
the macula and near the periphery. Also note
the presence of cotton wool spots inferiorly.
No exudate is present.

10. To confirm retinal elevation OD, you should order an OCT of the macula.

11. Note the
intraretinal
fluid very close
and temporal
to fovea

12. The 5-line
raster image
shows sub-foveal
cystoid
intraretinal
fluid

13. The OCT of
the macula in
the left eye is
normal, with
no edema or
exudate

15. Moderate NPDR OU
with CSME OD
What exactly does this mean? How do we classify what we see?

16. Diabetic retinopathy can be an alphabet soup.

17. Clinical Survival Guide
1. Quick review exam findings
2. Classification of CSME, NPDR, and PDR
3. Treatment Tools
4. Screening

18. Pericyte loss and basement membrane thickening
 occlusion
 retinal ischemia
Decompensation of endothelial barrier function
 serum leakage
 edema

19. EDEMA
Micro-aneurysms
& hemorrhage
Venous Beading
IRMAs
New Vessel Growth:
Disc, Retina, Angle

20. Focal: from a focal capillary lesion, e.g. MA
Diffuse: widespread capillary leak and
breakdown of blood-retinal barrier
Diagnosed on slit-lamp biomicroscopy!
Can be confirmed with OCT…

21. When edema is present (whether cystic, CME, or diabetic in origin, DME),
you must determine if it is clinically significant, as this influences treatment.
CSME was defined by the ETDRS group and there are three criteria. This is
somewhat painful to memorize. But basically, if edema is 1) CLOSE to fovea
2) not as close, but associated with exudate (old edema) 3) less close but
LARGE in size…it’s significant.

23. Enough about CSME for now. Let’s talk about the other things we may see with DR.
We must know these/recognize these in order to properly classify and treat DR.

24. Microaneurysms are outpouchings
of retinal capillaries

25. Ischemic damage to the
inner blood retinal barrer
 retinal hemorrhage.
These hemorrhages are
found in the inner
plexiform layer.

26. Flame hemorrhages conform
to the RNFL. They are another
type of small hemorrhage you
may see with DR. The above is
actually a CRVO, but it shows
excellent flame hemorrhages.

27. When you have intraretinal edema
and the RPE resorbs the aqueous
component at a faster rate than
the lipid plasma components,, the
result is accumulation of lipid
residues. Exudates may appear in a
circular pattern where the edema
was- like a ring on a bathtub. This is
what we classically described as
“hard exudates.” Soft exudates
were CWS, but now we know they
have a very different mechanism
so “hard exudates” are just
exudates.

28. retinagallery.com
Chronic retinal
ischemia leads to
architectural
changes in the
retinal vessels

29. - New vessel growth within the retina or remodeling of pre-existing
vessels through endothelial cell proliferation stimulated by hypoxia
bordering areas of capillary nonperfusion
-When compared to (NV), IRMAs are slightly larger in caliber with a more
broad arrangement and are always contained to the intraretinal layers

30. 3 Stage Evolution
1. Fine new vessels beyond ILM
 Minimal fibrous tissue
2. Increase in size/extent of vessels
 Increase in fibrous tissue
3. Vessel regression
 Residual fibrous tissue scaffolded to
posterior hyloid
http://www.lasereyecentre.co.ke/diabetic-retinopathy/

32.  One of the following:
 Mild NVD + VH
 Mod-Severe NVD +/-VH
 Mod NVE (≥ ½ disc area) with VH
 Three or more of the following:
 VH or pre-retinal hemorrhage
 Any active NV
 NV on or within one DD of the optic disc
 Mod-Severe extent of NV

33. Treatment Tools

34.  Focal- small leak
 light, small-sized burns to outside of the fovea
 Grid- diffuse leak
 grid or pattern of burns to the areas of macular
edema
Fluorescein angiography helpful to guide
treatment.

35. Anti-VEGF is quickly becoming FIRST LINE
Diabetic Retinopathy Clinical Research Network (DRCR.net)
- Ranibizumab (Lucentis) + prompt or deferred laser*
- More effective at improving VA through 1 yr than laser alone
Ranibizumab for Edema of the Macula in Diabetes 2 (READ-2)
- Laser
- Ranibizumab + laser (intermediate effect)
- Ranibizumab alone (7 letters better than laser alone)
RESOLVE, RESTORE, RIDE, RISE…

38.  Diabetes Control & Complications Trial (DCCT)
 Intensive therapy (Goal A1c < 6.05%) v Conventional
 How low is low enough?? There is a strong exponential relationship between
risk of DR and mean Hgb A1c
 For each 10% decrease in the hemoglobin A1c (e.g., from 9.0% to 8.1%),
there was a 39% decrease in the risk of progression of retinopathy
 NO glycemic threshold at which the risk of retinopathy was eliminated
above the nondiabetic range of hemoglobin A1c (4.0% to 6.05%).

39.  UK Prospective Diabetic Study (UKPDS)
 DM II assigned to tight control (<150/85
mmHg)

40. *
Very Severe**
* Risk of 1 yr. progression to PDR 50%, high-risk PDR 15%
** Risk of 1 yr. progression to PDR 75%, high-risk PDR 45%
Some patients have been called “very severe.” These patients,
with 2 of the severe NPDR classifiers, are at very high risk.

41. Consider early treatment with
Panretinal Photocoagulation (PRP)
ETDRS, Report 9:
In NPDR or non-high-risk PDR, early PRP v. deferral of photocoagulation
Findings:
1. Both groups had good outcomes
2. Early PRP not recommended for mild-mod NPDR
3. Early PRP, if performed, should be FULL PRP
4. Early PRP should be especially considered in DM II
For patients with severe NPDR, very severe NPDR or non-high-risk PDR…should we do PRP?
The decision often depends on the patient’s ability to follow up well, or if they have upcoming events like
pregnancy or cataract surgery

42. Anti-VEGF: ?? Role in PDR
 Numerous, mostly uncontrolled studies
 Temporarily decreases leak, NV regression
 Warning: rapid regression of NV  VH & RT/RD
Panretinal Photocoagulation (PRP)
 Mech: Decrease O2 consumption, Increase O2 diffusion
 (DRCR.net) no benefit in doing over multiple sessions

43.  Eyes with high-risk PDR had significantly
greater risk of severe visual loss (SVL) and
demonstrated the greatest benefit from PDR.
 PRP reduced SVL by at least 50%!!
 No clear benefit for PRP in eyes with severe
NPDR or non-high-risk PDR.

44.  VH and RD
 Adverse effects:
 Decreased-
▪ night vision
▪ color vision
▪ contrast sensitivity
▪ peripheral vision (treat nasal and superior last)
 Macular edema

45.  Guarded outcome s/p laser:
 Diffuse edema involving center of macula
 Diffuse fluorescein leak
 Macular ischemia
 Hard exudates in the fovea
 Marked cystoid macular edema
 Risks:
 Paracentral scotoma
 Increased edema (transient)
 CNV
 Subretinal fibrosis
 Scar expansion
 Inadvertent foveolar burns

46. Back to our patient:
We did get an FA for our patient. There was some question as to whether the fine,
frond-like vessels seen supero-temporally could be NV v. IRMA. There was also some
question as to whether or not laser would be appropriate given the degree of leakage.

49.  CSME and Non-Severe PDR
 Given aflibercept for the CSME
 Return 8 weeks
 Possible repeat aflibercept, possible focal laser

50.  It’s so important to remember that our patient came in to
clinic because of teleretinal imaging. Screening tools are key
for diabetic retinopathy. Traditional retinal fundus imaging
with a nonmydriatic camera typically takes 10 minutes. Dr.
Abramoff and colleagues just published an article describing
Iowa’s very own, IDP. It’s very cool! It is much faster and can
determine RDR.
 The IDP outputs the DR index (a dimensionless number
between 0 and 1 that expresses the likelihood that the
patient's images will show RDR) in less than 1 minute on
standard hardware…
 The goal is to increase the number of people who are screened
yearly, increase patient satisfaction, and reduce cost.

51.  Dr. Abramoff
 Dr. Kirkpatrick
 Dr. Weed
 VA Staff

52. - Abramoff MD, Folk JC, Han DP, Walker JD, Williams DF, Russell SR, et al. Automated analysis of
retinal images for detection of referable diabetic retinopathy. JAMA ophthalmology. 2013;131(3):351-
7.
- Bolz M, Lammer J, Deak G, Pollreisz A, Mitsch C, Scholda C, et al. SAVE: a grading protocol for
clinically significant diabetic macular oedema based on optical coherence tomography and
fluorescein angiography. The British journal of ophthalmology. 2014.
- DCRC.net. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt vs Deferred Laser
Treatment: 3-year Randomized Trial Results. Ophthalmology. 2012. 119(11): 2312-2318.
- De Venecia G, Davis M, Engerman R. Clinicopathologic correlations in diabetic retinopathy. I.
Histology and fluorescein angiography of microaneurysms. Archives of ophthalmology.
1976;94(10):1766-73.
- Early Treatment Diabetic Retinopathy Study Group. Fundus photographic risk factors for progression
of diabetic retinopathy. ETDRS Rep. No. 12. Ophthalmology 98, 823-833 (1991).
- Gregson PH, et. al. 1995.Automated grading of venous beading. Computers and biomedical
research; 28, 291-304.
- Shamsi HN, Masaud JS, Ghazi NG. Diabetic macular edema: New promising therapies. World journal
of diabetes. 2013;4(6):324-38.
- Wilkinson CP, Ferris FL, 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international
clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology.
2003;110(9):1677-82.