a total of 1380 eyes were treated with prp for the indication 
 of pdr from march 2001 to september 2006.the modified air 
 lie house classification was followed .
cases included pdr of 
 varying severity such as flat new vessels , with raised new 
 vessels , subhyaloid hemorrhage , vitreous hemorrhage , trd 
 and macular edema with and without vitreous traction .
thus in 
 some of these cases the clinical evidence of vitreous contraction27 
 was already present before laser treatment was applied . in 
 order to study the course of changes in the vitreous tissue over 
 long term , we selected 100 eyes photocoagulated for pure pdr 
 without clinically evident vitreous traction ( as defined below ) . out of these 100 eyes
74 eyes showing complete regression of 
 new blood vessels following prp were studied over a follow - up 
 period of one to four years .
criteria for pure pdr ( without clinically evident vitreous 
 traction ) : selection ( 1 to 5 ) and follow - up ( 6 to 7 ) . 

proliferative diabetic retinopathy with flat new vessels 
 on the disc ( nvd ) and /or flat new vessels elsewhere 
 ( nve ) .
27,28neither hemorrhage in the vitreous nor subhyaloid 
 hemorrhageno tractional edema of maculano previous ocular surgeryabsence of systemic hypertension and renal diseasefundus fluorescein angiography ( ffa ) proven regression 
 of new vessels aft er prp and no recurrence of new vessels 
 during a follow - up of at least one year.presence of other signs of involution in addition to regression 
 of new vessels such as decrease in venous dilatation , disc 
 pallor , disappearance of retinal hemorrhages .
29 
  proliferative diabetic retinopathy with flat new vessels 
 on the disc ( nvd ) and /or flat new vessels elsewhere 
 ( nve ) .
27,28 neither hemorrhage in the vitreous nor subhyaloid 
 hemorrhage no tractional edema of macula no previous ocular surgery absence of systemic hypertension and renal disease fundus fluorescein angiography ( ffa ) proven regression 
 of new vessels aft er prp and no recurrence of new vessels 
 during a follow - up of at least one year .
presence of other signs of involution in addition to regression 
 of new vessels such as decrease in venous dilatation , disc 
 pallor , disappearance of retinal hemorrhages .
29 careful history was obtained regarding duration of diabetes , 
 type of diabetes and any other systemic illness ( hypertension , renal 
 failure ) contributing to retinopathy , concurrent ocular disease 
 and any previous ocular surgery .
cases with such concomitant 
 pathology were not included in the study [ table 1 ] .
detailed ocular examination including indirect 
 ophthalmoscopy , slit - lamp biomicroscopy , macular examination 
 with three mirror contact lens / 90 d lens and ffa was done . 

optical coherence tomography ( oct ) was done in 32 eyes 
 with csme out of 57 eyes ( 2004 onwards ) to rule out vitreous 
 traction .
eyes with any evidence of vitreous traction before prp 
 were not included in the study .
pan retinal laser photocoagulation with or without focal 
 /grid macular photocoagulation was done in all the 100 eyes . 

green 532 and red 810 diode laser delivered through slit - lamp , 
 were used .
diode laser was preferentially used for macular 
 photocoagulation in the presence of lenticular opacities.30 a 
 mild grey whitening of retina was the end point of treatment 
 with spot size 200 to 300  and exposure duration of 0.1 to 0.25 
 secs , with power level adjusted to produce the desired reaction . 

the prp was 
 completed in three to four sittings at intervals of four to seven 
 days each ; mainster 165 panfundoscopic lens was used .
follow - up was available in terms of visual acuity and ocular 
 examination at the first week in all cases .
the ffa was done 
 at six weeks ( 18 cases ) , eight weeks ( 64 cases ) and 11 weeks 
 ( 18 cases ) .
seventy - four out of 100 eyes responded by way of complete 
 regression of new vessels with laser photocoagulation [ table 
 2 ] .
twenty - six eyes required further prp or other adjunctive 
 treatment . out of 57 eyes with macular edema visual 
 improvement of two lines or more was observed in 34 eyes , 
 stabilization of visual acuity in 11 eyes and drop of visual acuity 
 by one line or more in 12 eyes . sixteen out of these 74 eyes 
 required to undergo vitreo retinal surgery within a period of one 
 to four years after complete regression of new vessels following 
 laser photocoagulation [ table 3 ] .
other signs of regression of 
 pdr such as disc pallor , ghost vessels and reduced venous 
 dilatation were present in only 39 out of 74 cases .
incidence of pdr was significantly high in type i dm ( p 
 0.001 ) and was observed to increase with duration of dm ( p 
 0.001 ) [ table 1 ] .
incidence of pdr with and without csme was 
 significantly high in the age group 41 to 55 years ( p 0.05 ) and 
 also regression of pdr with prp ( p 0.001 ) [ table 2 ] .
indications 
 for vitreo retinal surgery were significantly higher in type i dm 
 ( p 0.01 ) , irrespective of age and duration of dm [ table 3 ] .
diabetes induces pathology throughout the body and also 
 in the vitreous via non - enzymatic glycation of proteins.7,10 
 advanced glycosylation end products ( ages ) have been 
 found to be elevated in the vitreous of diabetics along with 
 aggregation of collagen fibers and alterations in the cortex and 
 hyalocytes.8,31 the vitreous in diabetics shows glycated collagen 
 and increased amount of other proteins .
7 - 9,32 degenerative 
 vitreous changes occurring in diabetics at a much younger age 
 produce anomalous pvd , which has been said to help formation 
 of new retinal vessels.9,33 structural changes at the vitreoretinal 
 interface promote migration and proliferation of vasogenic cells 
 in the vitreous , consequent contraction can produce vitreous 
 hemorrhage and macular edema.12,34 advanced glycation end products correlate with glycemic 
 control and these reactive compounds form on dna , lipids and 
 proteins where they represent pathophysiological modifications 
 that precipitate dysfunction at a cellular and molecular level 
 in diabetics.10,34 though the term diabetic vitreopathy exists in the 
 literature it has not been used to address and identify the 
 pathological complex of diabetic retinopathy in any of the 
 existing classifications of diabetic retinopathy .
19 - 22 we suggest 
 that changes in the vitreous primarily due to diabetes mellitus 
 and occurring independent of diabetic retinopathy can be 
 called primary diabetic vitreopathy. the methods currently 
 available for examination of the vitreous in vivo including oct 
 give good information about the vitreo retinal interface but 
 not the vitreous body , therefore such changes in the vitreous 
 may not be easily detected clinically
. we may therefore also 
 call primary diabetic vitreopathy as subclinical diabetic 
 vitreopathy.33 the hallmark of pdr is development of new vessels .
the 
 growing vascular endothelium combines with the collagen of the 
 vitreous and gives it a contractile property.2,13,14 simultaneously 
 fibrous tissue developing along the new vessels lines up on the 
 posterior hyaloid , this also imparts contractile property to the 
 vitreous.11 contraction of the vitreous can pull new retinal vessels 
 to produce a bleeding in the subhyloid space to begin with [ fig . 
 1 ] .
if the bleeding is forceful or the vitreous largely liquefied this 
 blood can break into the vitreous tissue concurrently or later .
it 
 should be noted here that bleeding outside the tissue confines 
 of retina ( internal limiting membrane ) is produced by vitreous 
 contraction and not proliferative retinopathy per se and thus 
 any hemorrhage outside the retinal tissue whether subhyloid 
 or in the vitreous should be considered a sign of vitreopathy 
 and not retinopathy .
bleeding further augments the contractile 
 property of the vitreous by inclusion of vasogenic and fibrogenic 
 elements and such recurrent bleeding may result in the 
 formation of fibrovascular tissue in the vitreous cavity .
2 ] , secondary 
 rhegmatogenous retinal detachment , persistent macular edema , 
 premacular hemorrhage in addition to recurrent vitreous 
 hemorrhage.35,36 we propose to call the changes induced in the 
 vitreous tissue by proliferative retinopathy secondary diabetic 
 vitreopathy or clinical diabetic vitreopathy. these are mainly 
 in the form of an increase in the contractility and detachment 
 of the vitreous .
these changes are different from the changes 
 of primary diabetic vitreopathy. if total vitreous detachment was present before development 
 of pdr no bleeding or tractional retinal detachment may occur . 

similarly , if there was no separation of vitreous subsequent 
 to development of retinal new vessels the above pathological 
 events may not occur .
there have been several attempts in 
 the past for pharmacological vitreolysis so as to abort any 
 complications of retinal neovascularization by pull of vitreous 
 and there is a continuous suggestion in the literature for early 
 vitrectomy in pdr cases with good vision so as to forestall 
 the complications produced by vitreopathy .
37 - 39 however , the 
 changes in the vitreous have never been included in any of the 
 classifications of diabetic retinopathy .
laser ablation of the retina induces regression of new vessels 
 in about two - thirds of cases .
1 - 3 this results in the disappearance 
 of a ready source of bleeding i.e. new vessels . with laser 
 treatment the incidence of non - resolving massive vitreous 
 hemorrhage has drastically reduced .
but the other indications 
 for vitreo retinal surgery such as trd , rhegmatogenous retinal 
 detachment [ fig .
3 ] , tractional macular edema , premacular 
 fibrosis , small recurrent vitreous hemorrhages , retinal wrinkling , 
 macular heterotropia and dense premacular hemorrhage have 
 persisted .
4 - 6 , 15 - 18 these are all produced by vitreopathy , vitreous 
 traction and not by pdr alone . in our series , out of 74 eyes showing complete regression 
 of new vessels with prp , 16 eyes ( 23% ) required to undergo 
 vitreous surgery for the indications of recurrent vitreous 
 hemorrhage ( eight ) , tractional retinal detachment ( four ) 
 secondary rhegmatogenous retinal detachment(one ) and 
 tractional macular edema ( three cases ) [ figs.4 a , b , c ] .
in other 
 words 23% of cases showed a continued contraction of vitreous 
 strong enough to produce the indications for surgery despite 
 successful regression of new vessels .
we invited data from 
 leading retina centers in the country on incidence of vitreous 
 surgery in cases of pdr fully regressed with prp , over a period 
 of one to four years .
it is logical to say that in these cases the changes of primary 
 /secondary diabetic vitreopathy were relatively independent of 
 the effect of laser treatment and the regressed status of pdr . in 
 the remaining 77% cases
there are several factors which explain 
 the absence of complications produced by diabetic vitreopathy . 

regression of new vessels is withdrawal of a ready source of 
 bleeding , multiple chorioretinal adhesions produced by laser 
 protect against trd and rhegmatogenous retinal detachment . 

laser treatment in cases with csme helps resolution of edema , 
 it is effective in tractional macular edema also if the vitreous 
 traction is not very strong .
in addition to the above , prp induces 
 posterior vitreous detachment in 50% cases and in the large 
 majority this is eventless .
a small percentage of these cases 
 may show vitreous bleeding or even trd during completion 
 of prp if it is too aggressive and spaced closely.40 we therefore 
 understand that in the large majority of cases ( 77% in our 
 series ) a balance is established between the beneficial effect of 
 laser on retina and the damaging effect of diabetic vitreopathy . 
 in the remaining cases ( 23% in our series )
this balance might 
 not be established and ongoing vitreous contraction might 
 have produced indications for vitreo retinal surgery .
another 
 aspect of the effect of laser photocoagulation is that though the 
 new vessels disappear the fibrous tissue does not and a slow , 
 late cicatrization of fibrous tissue can produce indications like 
 retinal wrinkling , macular heterotropia41 and shallow trd ; 
 we had one such case in our series with retinal wrinkling and 
 trd occurring in regressed retinopathy after a quiet period of 
 three years [ fig .
we suggest diabetic vitreopathy as a separate subdivision 
 in the existing classification of diabetic retinopathy , identifying 
 the changes induced by diabetes mellitus as  primary diabetic 
 vitreopathy and the changes induced by pdr as secondary 
 diabetic vitreopathy. it is the changes of secondary diabetic 
 vitreopathy which can be clinically observed and which 
 produce the indications for vitreo retinal surgery , these can 
 be called diabetic vitreopathy as such or clinical diabetic 
 vitreopathy. we further observe that certain cases of clinical 
 diabetic vitreopathy might not be operable because of extensive 
 neovascularization both in the anterior and posterior segment 
 or many complex fibrovascular membranes in the vitreous . in 
 other words
we can have cases which are operable and may 
 benefit by vitreous surgery i.e. surgical vitreopathy and cases 
 which are inoperable or may not benefit by vitreous surgery 
 i.e. non surgical vitreopathy. recently , intravitreal drugs have been used to alter the course 
 of pdr .
first is 
 purified ovine hyaluronidase ( vitrase , ista pharmaceuticals ) 
 which produces vitreous liquefaction .
the second group are 
 anti - vegf drugs , which reduce neovascularization , contraction 
 of fibrovascular proliferations when prp is applied and 
 bleeding during surgery .
avastin ( genetech pharmaceuticals ) , 
 the commonest drug , has been used as a preoperative adjunct 
 for pdr , trd with severe pdr , for iris rubeosis , florid disc 
 neovascularization and for treatment of pdr complicated by 
 vitreous hemorrhage .
23 - 26 this would mean that anti - vegf drugs can be used 
 in cases which are either inoperable because of extensive 
 neovascularization , massive vitreous hemorrhage or are risky 
 to operate due to the possibility of intraoperative bleeding 
 and other complications .
use of these drugs may render such 
 cases suitable for surgery . in order to identify such cases in a 
 logical manner
we suggest a separate class in between surgical 
 and non - surgical vitreopathy as intermediate vitreopathy. 
 the cases put in this class can shift to the surgical vitreopathy 
 group if response to drug is adequate and to the non - surgical 
 vitreopathy group if the drug treatment does not make the 
 case operable .
the term diabetic retinopathy may be replaced by 
 diabetic retino - vitreopathy and may be classified as 
 below . 

non - proliferative diabetic retinopathy ( mild / moderate/ 
 severe / very severe)proliferative diabetic retinopathydiabetic maculopathy ( focal , diff use , ischemic , mixed)clinical diabetic vitreopathyi ) surgical vitreopathyii ) intermediate vitreopathyiii ) non - surgical vitreopathy 
  non - proliferative diabetic retinopathy ( mild / moderate/ 
 severe / very severe ) proliferative diabetic retinopathy diabetic maculopathy ( focal , diff use , ischemic , mixed ) clinical diabetic vitreopathy i ) surgical vitreopathy ii ) intermediate vitreopathy iii ) non - surgical vitreopathy 
 posterior pole trd 5superior half trd 16tractional macular edema without macular 
 ischemia 15premacular fibrosis 28recurrent vitreous hemorrhages in laser regressed 
 pdr 4 , 17secondary rhegmatogenous retinal detachement 27 - 28optic disc traction 27 , 28macular heterotropia 41retinal wrinkling 41dense premacular hemorrhage 35 
  tractional macular edema without macular 
 ischemia 15 premacular fibrosis 28 recurrent vitreous hemorrhages in laser regressed 
 pdr 4 , 17 secondary rhegmatogenous retinal detachement 27 - 28 optic disc traction 27 , 28 macular heterotropia 41 dense premacular hemorrhage 35 
 florid neovascularization with /without any of the above indications 26anterior segment neovascularization 24neovascularization non - responsive to laser
with/ 
 without any of the above indications   24 - 26large non - resolving vitreous bleeding in laser - treated 
 or untreated pdr 26 
  florid neovascularization with /without any of the above indications 26 anterior segment neovascularization 24 neovascularization non - responsive to laser with/ 
 without any of the above indications   24 - 26 large non - resolving vitreous bleeding in laser - treated 
 or untreated pdr 26 
 inferior peripheral trd 16recurrent vitreous hemorrhages in active pdr 28 , 36tractional macular edema with ischemia 15 , 27 
  inferior peripheral trd 16 recurrent vitreous hemorrhages in active pdr 28 , 36 tractional macular edema with ischemia 15 , 27 this classification represents all stages and manifestations 
 of diabetic retinopathy including changes in the vitreous .
the 
 classification identifies surgical indications and places different 
 manifestations in accordance with the pathology and indicated 
 treatment .
for example , tractional diabetic macular edema is 
 classified as surgical vitreopathy as it is the vitreous traction 
 which is the cause and surgery is the treatment .
the classification incorporates the indications for using 
 recent intravitreal anti - vegf drugs also .
the study sets the direction for further research and 
 investigations on vitreous changes using modern tools such as 
 ultrasound and oct in diabetics before and after development 
 of diabetic retinopathy and also long - term prospective 
 observations on the retina and vitreous on a larger sample 
 of pdr cases after prp .

 non - proliferative diabetic retinopathy ( mild / moderate/ 
 severe / very severe)proliferative diabetic retinopathydiabetic maculopathy ( focal , diff use , ischemic , mixed)clinical diabetic vitreopathyi ) surgical vitreopathyii ) intermediate vitreopathyiii ) non - surgical vitreopathy 
  non - proliferative diabetic retinopathy ( mild / moderate/ 
 severe / very severe ) proliferative diabetic retinopathy diabetic maculopathy ( focal , diff use , ischemic , mixed ) clinical diabetic vitreopathy i ) surgical vitreopathy ii ) intermediate vitreopathy iii ) non - surgical vitreopathy

 posterior pole trd 5superior half trd 16tractional macular edema without macular 
 ischemia 15premacular fibrosis 28recurrent vitreous hemorrhages in laser regressed 
 pdr 4 , 17secondary rhegmatogenous retinal detachement 27 - 28optic disc traction 27 , 28macular heterotropia 41retinal wrinkling 41dense premacular hemorrhage 35 
  tractional macular edema without macular 
 ischemia 15 premacular fibrosis 28 recurrent vitreous hemorrhages in laser regressed 
 pdr 4 , 17 secondary rhegmatogenous retinal detachement 27 - 28 optic disc traction 27 , 28 macular heterotropia 41 dense premacular hemorrhage 35

 florid neovascularization with /without any of the above indications 26anterior segment neovascularization 24neovascularization non - responsive to laser with/ 
 without any of the above indications   24 - 26large non - resolving vitreous bleeding in laser - treated 
 or untreated pdr 26 
  florid neovascularization with /without any of the above indications 26 anterior segment neovascularization 24 neovascularization non - responsive to laser with/ 
 without any of the above indications   24 - 26 large non - resolving vitreous bleeding in laser - treated 
 or untreated pdr 26

 inferior peripheral trd 16recurrent vitreous hemorrhages in active pdr 28 , 36tractional macular edema with ischemia 15 , 27 
  inferior peripheral trd 16 recurrent vitreous hemorrhages in active pdr 28 , 36 tractional macular edema with ischemia 15 , 27 this classification represents all stages and manifestations 
 of diabetic retinopathy including changes in the vitreous .
the 
 classification identifies surgical indications and places different 
 manifestations in accordance with the pathology and indicated 
 treatment .
for example , tractional diabetic macular edema is 
 classified as surgical vitreopathy as it is the vitreous traction 
 which is the cause and surgery is the treatment .
the classification incorporates the indications for using 
 recent intravitreal anti - vegf drugs also .
the study sets the direction for further research and 
 investigations on vitreous changes using modern tools such as 
 ultrasound and oct in diabetics before and after development 
 of diabetic retinopathy and also long - term prospective 
 observations on the retina and vitreous on a larger sample 
 of pdr cases after prp .
changes in the vitreous induced 
 by diabetes mellitus are identified as primary diabetic 
 vitreopathy / subclinical diabetic vitreopathy and changes 
 induced by proliferative retinopathy as secondary diabetic 
 vitreopathy / clinical diabetic vitreopathy .
any indications for 
 vitreous surgery in pdr are produced by vitreopathy and not 
 retinopathy per se . in about
two - thirds of pdr cases vitreopathy can be kept 
 under control with adequate prp , the remaining one - third cases 
 may require surgery due to vitreopathy .
a new classification 
 is proposed taking into consideration the element of diabetic 
 vitreopathy as well as the clinical use of intravitreal anti - vegf 
 drugs .
 background : many eyes with proliferative diabetic retinopathy ( pdr ) require vitreous surgery despite 
 complete regression of new vessels with pan retinal laser photocoagulation ( prp ) . 
 changes in the vitreous 
 caused by diabetes mellitus and diabetic retinopathy may continue to progress independent of laser regressed 
 status of retinopathy . 
 diabetic vitreopathy can be an independent manifestation of the disease process.aim:to examine this concept by studying the long - term behavior of the vitreous in cases of pdr regressed 
 with prp.materials and methods : seventy - four eyes with pure pdr ( without clinically evident vitreous traction ) 
 showing fundus fluorescein angiography ( ffa ) proven regression of new vessels following prp were 
 retrospectively studied out of a total of 1380 eyes photocoagulated between march 2001 and september 2006 
 for pdr of varying severity . 
 follow - up was available from one to four years.results:twenty-three percent of eyes showing ffa - proven regression of new vessels with laser required 
 to undergo surgery for indications produced by vitreous traction such as recurrent vitreous hemorrhage , 
 tractional retinal detachment , secondary rhegmatogenous retinal detachment and tractional macular edema 
 within one to four years.conclusion:vitreous changes continued to progress despite regression of pdr in many diabetics . 
 we 
 identifies this as  clinical diabetic vitreopathy  and propose an expanded classification for diabetic 
 retinopathy to signify these changes and to redefine the indications for surgery . 