Diabetic retinopathy is managed through modification of systemic risk factors like blood sugar and blood pressure control, as well as ocular treatments. Laser photocoagulation and intravitreal anti-VEGF injections are primary treatment modalities. Laser photocoagulation through panretinal or macular grid lasers is effective for proliferative diabetic retinopathy and diabetic macular edema respectively. Intravitreal anti-VEGF drugs like ranibizumab, aflibercept and bevacizumab are effective treatments for center-involving diabetic macular edema and can be alternatives to laser in some cases. The choice of treatment depends on the severity and location of retinopathy and macular edema.

1. DIABETIC RETINOPATHY
MANAGEMENT
DR.PRAKRITI YAGNAM .K
MODERATOR : DR.CH.MOHAN RAO

2. Management of Diabetic retinopathy :
ü Diagnostic imaging modalities
ü Modification of systemic risk factors
ü Ocular treatment modalities
ü Screening , surveillance and follow up

3. Diagnosis and imaging modalities :
• Slit lamp biomicroscopy and Ophthalmoscopy
• Color fundus photograph
• Wide field imaging
• FFA
• OCT and OCTA
• B scan ultrasonography
• Anterior segment evaluation to rule out complications

4. Indications for FFA :
• Disproportionate visual loss
• Suspected neovascularization
• DME : Focal or diffuse and ischemic or non ischemic
• Non responsiveness to treatment
• Guide for laser treatment
Limitations :
• FAZ becomes fuzzy and difficult to determine size

6. DME :
• Focal : A single or localized clusters of leakage sites with hard exudates
• Diffuse : Generalized leakage from blood vessels throughout posterior pole
Ischemic maculopathy :
ü Enlarged and irregular Foveal Avascular Zone ( FAZ )
ü Dilated and tortuous capillaries budding into FAZ
ü Terminal arterioles or venules directly abutting the FAZ
ü Enlarged inter capillary spaces around FAZ

9. OCT :
• Enable to detect morphological changes
• Retinal thickness and volume and surface area
• Diagnosing and monitoring progression of DME
• Helps in qualitative and quantitative analysis
• Serves as a guide in laser treatment
• Follow up of disease course

10. Hyper reflective lesions : Hypo reflective lesions :
• Hard exudates
• Cotton wool spots
• Inflammatory foci
• Intra retinal edema
• CME
• Neuro sensory detachment
Shadow effect :
• Hemorrhages
• Hard exudates
• Retinal vessels

12. Focal or Diffuse without
cysts
Cystoid edema Serous retinal detachment
• Increased retinal
thickness
• Subtle spongy intra
retinal changes
• Intracellular fluid
• Accumulation of extra
cellular fluid within
cavities or cysts
• Accumulation of fluid
within sub
neurosensory space
DME :
• Taut posterior hyaloid and VMT can also be noted
• Thinning of fovea is noted in macular ischemia

15. OCT – A :
•Studies retinal , choroidal and
optic disc vasculature
•MAs , IRMAs ,venous changes ,
CNP areas , FAZ , NVD , NVE can
be noted
Limitations :
•Leakage not seen
•Slow flow may be missed
•Projection and motion artifacts
may decrease the quality

16. Biomarkers in OCT and OCT – A :
Good prognosis Poor prognosis
• Initial CSF thickness
• Retinal processes
• Decrease in intraretinal cysts
• Decrease in Neuro sensory
detachment
• DRIL
• Disrupted ELM / IS – OS layer
• Loss of parallelism
• Decreased reflectivity of ellipsoid zone
• RNFL thinning
• ORT
• Hyperreflective dots – inflammatory
foci
• Enlarged FAZ

18. Wide Field Imaging :
• Traditional imaging has limited field of view
• Most of the peripheral lesions could not be assessed
• So wide field helps in early detection of peripheral NVE
• Localization and quantification of peripheral non perfusion areas ( anterior to equator )
• Guide to targeted retinal photocoagulation

20. Modification of systemic risk factors :
Hyperglycemia control :
• It is critical in minimizing risk of onset and progression of diabetic retinopathy
• ADA recommends glycemic control targeting a HbA1C < / = 7 %
• Studies include DCCT , EDIC , UKPDS , ACCORD
ACCORD - Action to Control Cardiovascular Risk in Diabetes
• Benefit of further reduction of HbA1C below 6 % in type 2 DM but is associated with higher mortality
rates

21. DCCT – Diabetes Control and Complications Trial :
• Intensive glycemic control was associated with reduced risk of a new onset of retinopathy and reduced
progression to severe NPDR and PDR , incidence of DME and need for photocoagulation in type 1 DM
UKPDS - United Kingdom Prospective Diabetes Study :
• With HbA1C less then 7 % onset and progression of retinopathy is reduced in type 2 DM

22. Other factors :
• Hypertension control
• Dyslipidemia control
• Cessation of smoking
• Anemia management
• Renal failure management

23. Systemic assessment :
• FBS , PPBS , HbA1C
• BP
• Lipid profile
• Hb
• RFT

24. Ocular Treatment modalities :
• Intra vitreal anti VEGFs
• Intra vitreal steroids PRP
• Laser photocoagulation
• Focal / Grid
• Surgery - Vitrectomy

25. Pan retinal photocoagulation :
• Also called scatter photocoagulation
• It is a thermal laser photocoagulation technique ( blue or blue – green lasers )
• Gold standard of treatment for severe NPDR and PDR without DME
• Definitive treatment for NVI and NVA
• But now anti VEGFs or combined therapies are also given depending upon the circumstances
• If coexistent DME is present it is treated prior to PRP or in same sitting with focal or grid laser or
antiVEGFs
• Studies which demonstrated benefits of PRP - DRS and ETDRS

26. DRS study :
ü Photocoagulation ( argon or xenon ) reduces risk of severe vision loss compared with no treatment
ü Treated eyes with high risk PDR achieved greatest benefit
ETDRS study :
ü Early PRP resulted in small reduction in severe vision loss ( < 5/ 200 for 4 months )
ü Most effective for type 2 DM patients and not indicated for mild to moderate DR

27. Mechanism of action :
• Decreases production of vasoproliferative factors by eliminating areas of hypoxic retina
• Decreases oxygen consumption over all as a result of purposeful retinal destruction
• Increases the diffusion of oxygen from the choroid in the areas of photocoagulation scars
• Increases vasoinhibitiors by directly stimulating the RPE
• Decreases choroidal circulation in the periphery thus directing more flow towards the centre – reverse
choroidal steal
Goal :
Regression of existing neovascular tissue and prevent progressive neovascularization

28. Procedure :
• Informed consent is taken
• Topical anaesthesia ( 0.5 % proparacaine ) applied and mydriasis ( Tropicamide 1 % + Phenylephrine 5 % )
done
• Anti glaucoma medication ( 0.15 % Brimonidine ) one hour before the session to prevent post PRP iop
spikes
• Lens - Panfundoscopic lens ( Rodenstoch ) , Volk Super Quad lens , Goldmann lens or Mainster lens

29. Parameters :
ü Laser : Argon blue or blue green laser ( 514 nm. )
ü Spot size : retinal burn diameter of 400 – 500 microns
with panfundoscopic lens 200 microns is selected , Goldman – 400 microns
ü Duration : argon laser - 0.05 to 0.1 sec.
newer laser – 0.001 to 0.05 sec.
ü Power : 200mW – adequate to produce only light intensity burns
ü Spacing : Burns separated by 1 – 1.5 burn width

31. Extent of treated area :
• According to DRCR.net guidelines maximum extent ( DR Clinical Research )
Nasally - ½ DD or 500 microns
Temporally - 3000 microns or twice the distance between disc and macula
Superior and inferior - Superior and inferior arcades
Anteriorly - Vertex ampulla or equator
• In high risk PDR inferior retina must be coagulated first to prevent view obstruction later on due to any
bleed during the procedure

33. • Treatment may be accomplished in single or multiple sessions ( 4 – 5 ) with 1 – 2 weeks interval
between
• According to DRCR.net no long term vision benefit of multiple sessions over single session
• More extensive treatment at single session result in more complications
• In most cases initial treatment has 1200 – 1500 burns
• Average burns required for regression :
mild PDR - 2500 to 3500
moderate - 4000
severe - 7000

34. Post laser advice :
• Topical cycloplegic ( 1 % cyclopentolate ) TID for three days
• Topical steroid TID for three days
• Tab . Acetazolamide 250 mg. if there is IOP spike
Review :
• Depends on PDR severity
• Once adequate number of burns is applied follow up done after 4 – 6 weeks for 3 months and then
every three months

35. Indicators of
regression:
Blunting of vessel tips
Shortening and disappearance of new
vessels – leaving ghost vessels or fibrosis
Regression of IRMA
Decreased venous changes
Absorption of retinal hemorrhages and disc
pallor

36. Complications :
Vitreous
hemorrhage
( Due to contraction of
regressing vessels )
Tractional
retinal
detachment
( Areas of VMT must
be avoided )
Central and
paracentral
scotomas ( 2
DD nasal retina to
fovea left free to
avoid paracentral
scotomas )
Decreased
color vision
and dark
adaptation
Decreased
near vision(
Spasm of long ciliary
nerves )
Damage to
Cornea ,
lens , iris ,
pupillary
dilatation
Macular
edema ,
Choroidal
detachment
, CNVM (
Damage to blood
retinal barrier )

37. Macular
Grid lasers :
Used in macular edema
Gold standard for Non center
involving DME
First described by Patz –
argon laser photocoagulation
decreases or stabilizes
macular edema
Focal laser

38. According to ETDRS protocol : FFA guided
Focal laser Grid laser
Applied directly to microaneurysms in
area of retinal thickening between 500
– 3000 microns
Applied to areas of retinal thickening or
areas of capillary non perfusion between
500 – 3000 microns from fovea
Modified grid – treating foci of leakage
• Spot size is 50 – 200 microns.
• Exposure time is 0.05 to 0.1 sec. and energy 50mW
• Argon green laser ( 514 nm. ) or diode laser is used

40. Post laser advice :
Similar to PRP
Follow up :
• First followup in 4 weeks
• Second in 3 to 4 months
• Retreatment done in second followup if there is persistent focal or diffuse leakage

41. Review :
• Done after 4 weeks and if inadequate can repeat after 4 months
Results :
• 33 % treated with focal / grid photocoagulation improved by 10 or more letters at 2 years of age
• 50 % still had evidence of central edema at 2 years
• So there is a need for effective therapy for DME

42. ETDRS study :
• Focal photocoagulation for DME decreased risk of moderate vision loss
• Increased chance of moderate vision gain
• Reduced retinal thickness
Complications:
• Accidental foveal burn or damage with decreased color vision and contrast sensitivity
• Aggravation of macular edema
• CNV
• Paracentral scotoma

43. Sub threshold micro pulse
diode laser :
Very short micro second
order laser pulse
duration combined with
a longer interval
Ex : 5 % duty cycle
Allows energy
dissipation , minimizing
collateral damage to the
retina , whilst
stimulating the RPE
Pattern lasers :
10msec. laser spots that
reduce retinal edema
with minimization of
scar formation

44. Summary for laser photocoagulation :
• DRS and ETDRS conclusively proved that timely laser photocoagulation of DR reduces severe visual
loss by 95 %
• Laser is the treatment of choice for CSME not involving the fovea

45. Anti VEGFs :
• Considered the primary treatment in the
fovea involving DME in most eyes
• Has superior beneficial effect as compared to
laser and steroids with relatively good safety
profile
Drugs available are :
• Bevacizumab - Avastin
• Ranibizumab - Lucentis
• Aflibercept - Eyelea
• Pegaptanib - Macugen

46. VEGF :
• It is a dimeric glycoprotein that stimulates proliferation , migration leading to angiogenic growth of
new blood vessels
• It has seven different alleles : VEGF – A , B , C , D , E , F and PIGF
• VEGF – A is the most important of all
• RPE , astrocytes , muller cells , endothelial cells and ganglion cells can secrete VEGF
• In hypoxic conditions there will be overstimulation of VEGF resulting in PDR changes

47. Bevacizumab Ranibizumab Afibercept Pegapatanib
Monoclonal antibody
Binds all VEGF – A isoforms
Humanized monoclonal Ab
fragment
Non selectively binds and
inhibits all isoforms of
VEGF - A with higher
affinity than Bevacizumab
Recombination fusion
protein
Binds to VEGF - A , VEGF -
B and Placental growth
factor
Aptamer
Binds specifically only one
VEGF – A isoform
1.25 mg. in 0.05 ml. once
in every four weeks
0.5 mg./0.05 ml. once in
every four weeks
2 mg./ 0.05 ml.
Monthly for three months
and then every two
months
0.3 mg. once in every six
weeks
Off label drug Safety profile studied in
MARINA and ANCHOR
studies
Newer drug Only FDA approved drug

49. Indications in PDR :
Persistent VH ( After
RD is ruled out by B
scan )
Initial treatment of
rubeosis irides whilst
a response to PRP is
realized
Rapid control of very
severe PDR to
minimize risk of
haemorrhage
Preoperatively as n
adjunct to vitrectomy
to manage
complications of PDR

50. Studies :
1. DRCR.net Protocol S study –
• Intravitreal Ranibizumab non inferior to PRP in visual acuity outcomes at two years in patients with
active PDR
• Less field loss and lower rates of vitrectomy , VH and TRD are the benefits
• But patients must be on regular treatment
Conclusion :
• Although Ranibizumab is superior to PRP , it depends on patients adherence to treatment
• Non adherent patients due to medical or other limitations must be considered for PRP

51. Indications in DME :
• First line in all centre involving DME especially those with vision impairment caused by DME
• Studies include –
ü Protocol I
ü RISE and RIDE
ü RESTORE Ranibizumab for DME
ü RESOLVE
ü REVEAL and RETAIN

52. Protocol I :
• Intravitreal Ranibizumab with prompt or deferred focal / grid laser superior to laser treatment alone
or with combination with IVTA
RISE and RIDE :
• Ranibizumab Injection in Subjects With CSME With Center Involvement Secondary to Diabetes
Mellitus
• Ranibizumab rapidly and sustainably improves vision , reduces the risk of further vision loss and
improves DME

53. Aflibercept :
ü VIVID - Intravitreal Aflibercept Injection in Vision Impairment Due to DME
ü VISTA - Study of Intravitreal Aflibercept Injection in Patients with DME
ü DA VINCI
• Eyes received IAI every 4 weeks or every 8 weeks after five monthly doses found superior to laser
• Also had positive effects on DRSS score

54. Bevacizumab :
ü BOLT study
• High efficacy in center involving DME when compared to laser

55. Protocol T :
• Comparisons of efficacy between Ranibizumab , Bevacizumab and Aflibercept for DME – vision gain at
two years
• If initial VA is mild ( 20/32 to 20/40 ) - No difference
• If moderate to severe ( 20/50 or worse ) - Aflibercept = Ranibizumab
• Aflibercept is superior to Bevacizumab
Over all : Aflibercept > Ranibizumab > Bevacizumab

56. Treatment regimen :
• Monthly injections till 6/6 and OCT is dry or Stable ( VA / OCT unchanged in last two to three visits )
• PRN if DME recurs or worsens
• Treat and extend
• Can add focal laser initially
• Grid laser can be performed as rescue if poor response to anti VEGF

57. Complications :
• More for the technique rather than the drug - Iatrogenic
ü Endophthalmitis ( 1 in 1000 injections )
ü Lens touch
ü Vitreous hemorrhage
ü Retinal detachment
Drug related -
ü Systemic thromboembolic events - less common with intravitreal usage
ü Retinal toxicity and necrosis and inflammation mimicking infection
• Better to avoid in pregnancy

58. Intravitreal Steroids :
Indications :
• Recalcitrant or Persistent DME ( 3 inj . of anti VEGF and no response )
• Vitrectomized eyes with macular edema
• Patients requiring reduced treatment burden
• First line in pseudophakics
• Recent stroke / MI
• Pregnancy

59. Drugs :
ü Triamcinolone acetonide ( IVTA )
ü Flucinolone acetonide
ü Dexamethasone
• Efficacy present but do not show superiority to anti VEGFs or laser when used as monotherapy
Side effects -
• Cataract formation
• Rise in Intra Ocular Pressure

60. Dosages :
• IVTA - 4mg/0.1ml.
• Flucinolone implant - 0.2 micrograms/day. ( for more than one year )
( Illuvien )
- must be used in patients who have shown no rise in IOP
previously when steroids are used
- Non biodegradable
- Others - Retisert
• Dexamethasone implant - Ozurdex - 700 micrograms –
- Biodegradable

61. Studies :
• Bevordex study
• MOZART study - Multicenter Ozurdex Assessment for DME

62. Protocol U :
• Patients on Ranibizumab therapy did not benefit from addition of dexamethasone implant
• Addition of IVTA to Avastin offers no significant advantage
Protocol B :
• Treatment with grid or focal laser photocoagulation more effective than 1mg. Or 4 mg. of preservative
free triamcinolone
Protocol V :
• ci – DME with good vision ( > 20/ ) - observation better than cost of treatment

64. Vitrectomy :
• Plays a vital role in the management of complications of DR
Indications –
• Severe persistent VH - that precludes adequate PRP ( do not resolve within 3 months or bilateral VH or
monocularity )
• Progressive FVP
• Progressive threatening macular involving TRD - Extramacular , can be observed
• Combined TRD and RRD
• Premacular retrohyaloid haemorrhage - early vitrectomy with hyaloidectomy

65. Less
common:
Macular edema with thickened and taut
posterior hyaloid
Anterior hyaloid FVP ( common in young ,
phakic diabetics )
Epiretinal membrane
Severe preretinal macular heamorrhage
Neovascular glaucoma with cloudy media
Ghost cell glaucoma

66. Goals of surgery :
• Clear the media
• Release of all anterior - posterior and tangential vitreous traction by segmentation and delamination
techniques
• Complete PRP ( to reduce hypoxia )
ü Early vitrectomy ( in the absence of VH ) is not beneficial
ü VA < 5/200 for more than six months in type 1 DM – early vitrectomy

67. Settings of PPV :
• 20 to 27 gauge vitrectomy instrumentation
• 27 gauge provide sutureless surgeries ( MIVS – transconjunctival micro incision vitrectomy )
• Vitreous cutter – 1500 to 5000 – 7500 cuts / min cutting speed
• Intra ocular illumination – fibre optic probe with halogen or xenon bulbs
• Others - Infusion cannula , wide angle viewing systems and accessory instruments

68. Tamponading agents :
• Expanding agents - SF6 ( 20 to 30 % ) , perfluorethane ( C2F6 ) , perfluoropropane ( C3F8 - 12 to 16 % )
• Silicone oil ( 1000cs or 5000cs )
• Heavy liquid - perfluorocarbons

69. Procedure :
Infusion cannula ( at inferior border of LR insertion after insertion )
Sclerotomies at 2 and 10 ’ 0 clock for cutter and fibre optic probe
Central vitreous gel and posterior hyaloid face are excised
FVP - Release trans vitreal traction and tangential traction ( membrane dissection )
TRD – Release AP and circumferential VRT by delamination and segmentation
Endophotocoagulation and Internal tamponade

71. Complications :
• Raised IOP – Due to tamponading agents
• Glaucoma
• Cataract
• Band keratopathy

72. Prognosis :
Good Poor
• Small areas of traction • Table top detachments
• Significant preop hemorrhage
• No prior PRP
• Advanced FVP

73. Causes of failure :
NVI – NVG ( risk
higher if present
preoperatively )
Persistent RD after
surgery
Lens removed
during surgery
If there is florid
NVD

74. Pathogenesis of NVI :
Removal of vitreous
oxygenation posteriorly Hypoxic retina
O2 tension in anterior chamber Vasoproliferative factors diffuse
forward to iris
NVI
• If eye does not develop NVI in first 4 -6 months they rarely do after

75. • If vitrectomy cannot be performed B scan must be performed in regular intervals to make sure that
TRD is not developing behind the vitreous hemorrhage
• In patients who have recurrent VH after surgery a simple outpatient air – liquid exchange may
restore vision without need for vitrectomy

76. DME :
• In cases of posterior hyaloid traction or an associated ERM leading to mechanical traction , creation of a
posterior vitreous detachment and possible ILM and ERM peeling can be effective in reducing retinal
thickening
Protocol D :
• After vitrectomy retinal thickening was reduced in most eyes but median VA remained same

77. Additional therapies :
• Fenofibrate treatment causes reduction in progression of DR in type 2 DM ( ACCORD and FIELD
studies )
• Induction of PVD might improve outcome in eyes with risk of developing PDR
• Inhibition of protein kinase C that activates VEGF reduces risk of macular edema
Ex : Ruboxustaurin
• Inhibition of Angiopoietin 2 may also help
• Aspirin use dose not alter progression of DR or increase risk of VH or affect VA
( ETDRS )

78. Cataract surgery in patients with DR :
Protocol P : Patients with NPDR without DME may develop DME postoperatively
Protocol Q : With pre existing DME small percentage had substantial vision loss
Measures :
• ci – DME : Preoperative anti VEGF or perioperative steroid is given
• Severe NPDR or PDR : PRP before surgery if adequate view
If not immediate postoperative treatment
• Intraoperative measures : Adequate CCC to avoid anterior capsular phimosis
Avoid silicone lenses

79. Summary :
Grade Management
Mild to Moderate NPDR( without DME ) Observe
Severe NPDR and PDR PRP / Anti VEGFs / Combination
DME non ci Focal or Grid Laser / Anti VEGFs /
Combination
ci Anti VEGFs with prompt or deferred laser
Recalcitrant Steroids
Complications PPV

80. Screening and followups :
• Initial eye examination Type 1 DM – five years following diagnosis
Type 2 DM - At the time of diagnosis
Followup –
No retinopathy - yearly
Mild to moderate without DME - 6 to 12 months
severe NPDR and PDR - every 2 to 4 months
DME - monthly

81. Pregnancy :
• Prior to conception and early during first trimester
• No , mild or moderate DR – depending on severity and progression
• Severe DR - 1 to 3 months
• DME - more frequent

84. THANK YOU !!!