Diabetic retinopathy is one of the prima causes of sightlessness in the universe. From the informations collected from countrywide surveies, tendencies show that Diabetes mellitus is on the addition and seems to be emerging as a major public wellness job ( 1 ) . The job we now face in India is that despite modernizations and implementing western civilizations taking to an addition in sedentary life manner and ingestion of high fat nutrients, cognition about the disease and early diagnosing is still missing. In add-on, Asians surely have alone clinical and biochemical abnormalcies like, greater abdominal adiposeness, lower adiponectin levelsand increased insulin opposition. ( 2 ) Western literature have shown that 20 old ages after the start of diabetes, bulk of patients with type I diabetes ( insulin-dependent ) and more than 60 % of those with type II diabetes ( non-insulin dependant ) will hold a grade of retinopathy. ( 3 )
Merely as Asiatics have certain phenotypical sensitivities for developing Diabetes, this construct can be carried to other physiological features such as haemodynamics, in peculiar our subject of involvement, which is optic blood flow and its ordinance both in disease and wellness. A great trade of research and resource has been poured into placing the pathogenesis of Diabetic retinopathy. The blood supply to the outer retinal beds is from the choroidal vass and the interior retinal beds are supplied by the retinal capillaries which are supplied by the cardinal retinal arteria. Damaging effects of inveterate elevated glucose on the retinal capillary endothelial cells and pericytes and besides focal ischaemia as pathogenetic factors in patterned advance of disease have been good studied ( 4 ) . The cellular and biochemical mechanisms that cause diabetic vasoconstriction and vasodilation are besides get downing to be ascertained. However there are really few surveies that have looked at choroidal blood flow as a predictive or pathogenetic factor in the development and patterned advance of Diabetic Retinopathy.
The survey of the choroid is being looked into as an effort to reply some of the inquiries sing the pathogenesis of diabetic retinopathy and how these alterations are brought about in the retina. The pulsatile optic blood flow ( POBF ) and optic pulsation amplitude ( OPA ) are indirect indexs of choroidal blood flow. Though illations have been made from the few surveies that have been done on choroidal blood flow, decisions based on each survey have been contradictory to each other. With the coming of new and more accurate measuring tools, more dependable informations can be obtained sing the choroidal circulation and its perfusion.
Ocular blood flow can be indirectly measured non-invasively with the pneumotonometer, which measures the pulsatile optic blood flow and more late, the Dynamic Contour Tonometer which measures the optic pulsation amplitudes. These instruments provide the clinician with informations that can be used to construe the choroidal blood flow, which really supplies 80 % of the retina. ( 5 )
Dynamic contour tonometry ( DCT ) is a non-invasive technique of look intoing the intraocular force per unit area. It besides measures the optic pulse amplitude of the oculus being studied at the same time. Ocular blood flow varies with systole and diastole. The pulsatile optic blood flow ( POBF ) shows a extremum during systole. The difference in the lower limit and maximal values of the pulsatile wave contour during systole and diastole gives us the optic pulsation amplitude ( OPA ) .
In this survey, we focused on documenting optic pulsation amplitudes, and indirectly the choroidal blood flow, in diabetic patients with assorted phases of Diabetic retinopathy. We besides wanted to detect the consequence of high blood pressure on choroidal blood flow in Diabetic patients. By transporting out this survey, we may find whether alterations in choroidal blood flow play a function in either predicting diabetic retinopathy, or whether it proves to be a factor able to foretell patterned advance of diabetic retinopathy.
To document the optic pulsation amplitudes in patients with assorted phases of Diabetic retinopathy
1. To document any difference in Ocular Pulse Amplitudes with increasing badness of Diabetic retinopathy
2. To document any difference in Ocular Pulse Amplitudes between Diabetics with and without systemic High blood pressure
Reappraisal of literature
Burden of Diabetes Mellitus:
Harmonizing to WHO, 346 million people in the universe have diabetes. ( 1 ) The figure may turn to 438 million by 2030, which is 7.8 % of the grownup population. In 2004, around 3.4 million people died from complications related to diabetes mellitus ( 1 ) . More than 80 % of diabetes deceases occur within low- and middle-income states. The World Health Organisation ( WHO ) says that diabetes deceases will duplicate between 2005 and 2030. Non-communicable diseases, which includes diabetes, history for 60 % of all deceases worldwide. ( 1 ) While the planetary prevalence of diabetes is 6.4 % , WHO undertakings that the prevalence varies from 10.2 % in the West to 3.8 % in Africa. ( 1 ) 70 % of the current instances of diabetes occur within low- and in-between income states. With an estimated 50.8 million people populating with diabetes, India has the universe ‘s largest diabetes population, followed by China with 43.2 million.
In developing states, for every patient who is diagnosed with Diabetes, there is one patient who has the disease but has non been screened for it ( 3 ) . Without timely diagnosings and equal intervention, complications and morbidity from diabetes will lift exponentially.
80 % of type 2 diabetes is preventable by increasing physical activity, altering diet and bettering the environing environment. Yet, the incidence of diabetes is likely to lift globally ( 1 ) .
Economic load of disease:
The fiscal load caused by people with diabetes and their households depends on the economic position and the insurance policies of their states. In the poorest states, people with diabetes and their households bear the whole cost of the medical attention they can afford.
Diabetic retinopathy in India:
The prevalence of Diabetic Retinopathy in the Chennai Urban Rural Epidemiology ( CURES ) Eye Study in South India was 17.6 per cent where 1715 diabetic topics studied. This was a population based survey from 10 zones in Chennai, which included a representative sample of the population of 26,000 persons. Diabetes was diagnosed based on the past medical history, medicines for diabetes. The survey showed that the systemic hazard factors for oncoming and patterned advance of Diabetic Retinopathy are mainly continuance of diabetes, grade of glycaemic control and lipemia. ( 6 ) Among the 1715 known Diabetics, the overall prevalence of Diabetic retinopathy was 20.8 per cent, while among the freshly diagnosed diabetic topics 5.1 per cent had retinopathy. Higher frequence of all the classs of retinopathy ( overall, NPDR and PDR ) was observed in known diabetic topics compared to freshly detected instances. Prevalence of Diabetic macular hydrops in the entire diabetic population was 5.0 per cent and in the known diabetic topics it was 6.3, 1.1 per cent among the freshly diagnosed diabetic topics. ( 6 )
In another survey, R P Agrawal et Al ( 7 ) found that 1176 patients ( 28.9 % ) had grounds of Retinopathy out of 4067 patients with Diabetess who presented to an outpatient diabetic clinic. Out of this, there were 938 ( 79.8 % ) patients of non proliferative diabetic retinopathy ( NPDR ) , 68 ( 5.8 % ) patients of maculopathy and 172 ( 14.6 % ) patients of proliferative diabetic retinopathy. ( 8 )
R Raman et Al. ( 9 ) did a multicentric random sampling of the population in Chennai for testing for diabetic retinopathy. The sample size was 5900. They found the prevalence of Diabetes to be 28.2 % and the prevalence of diabetic retinopathy to be 3.5 % . ( 9 )
Ramachandran A et Al ( 9 ) conducted a survey among 3010 topics ( M: F 1892:1118, Mean age 52 +/- 9.7 old ages ) go toing an outpatient diabetic clinic. The survey sample resembled the population sample. Retinopathy was diagnosed in 23.7 % ( nonproliferative retinopathy in 20.0 % and proliferative in 3.7 % ) . ( 10 )
Pathophysiology in Diabetic retinopathy:
Diabetic retinopathy is basically a microangiopathy in which there is escape in the blood retinal barrier, ensuing from harm to the walls of the arteriolas providing the retina. Hyperglycaemia leads to a broad assortment of microvascular and macrovascular abnormalcies, including unnatural autoregulation. ( 9 ) As described by Ciulla et Al. , chronic hyperglycaemia leads to change retinal vasoregulations. This increases bulk retinal blood flow with progressive retinopathy, perifoveal capillary dropout. In bend, there are retrobulbar hemodynamic abnormalcies, including choroidal, cardinal retinal arterial flow alterations and ophthalmic arterial flow changes. ( 9 ) Having said that, the factors that link raised glucose degrees to capillary dropout, vascular cell disfunction, and tissue hypoxia have non been elucidated.
Ocular blood flow response to hyperglycaemia:
With respect to the macrovascular pathophysiology, Bursell et Al ( 9 ) found that chronic hyperglycemia is associated with a lessening in retinal blood flow, but the retina is still capable of autoregulating this by increasing retinal blood flow harmonizing to the acute lifts in blood glucose. Their survey with video fluorescent dye angiography ( n=60 ) suggest that every bit compared to normal optic blood flow, there is a lessening in optic blood flow in diabetic patients without Diabetic retinopathy. When patients had been exposed to acute addition in glucose degrees, there was an addition in retinal blood flow within one hr. The retinal blood flow with progressively increasing sugar degrees were as follows: with the glucose clinch at 100 mg/dl, the retinal blood flow was 16.3 3.8 AU ( arbitrary units ) ; with the Glucose clinch at 200 mg/dl: 21.5 4.7AU, with the glucose clinch at 300 mg/dl: 25.9 8.8 AU and in the Random diabetic group, it was 19.4 4.6 AU. In the non diabetic group: 28.7 6.4 AU. They suggest that chronic hyperglycemia is associated with decreased retinal blood flow, but that the retina is still capable of reacting to increased metabolic rates associated with acute alterations in blood glucose by increasing retinal blood flow.
Retinal blood flow surveies:
Different surveies have found different consequences of increased, decreased or no alterations in the optic blood flow in different phases of retinopathy.
Kohner et Al ( 11 ) studied retinal blood flow in 9 normal voluntaries and 36 diabetic patients utilizing video fluorescent dye angiography. Measurement of the average theodolite clip of flourescein in the superior temporal quandrant of the retina and appraisal of the vascular volume by mensurating vass diameters was done. The consequences showed that patients with mild or no retinopathy had significantly increased volume flow compared with conventions, those with moderate retinopathy had a little but non important addition and those with terrible retinopathy had blood flow similar to that found in conventions.
Clermont et Al ( 12 ) showed that the retinal blood flow increased as the phase of retinopathy increased. In this survey, 48 diabetic and 22 nondiabetic patients had their diabetic retinopathy degrees determined from fundus exposure harmonizing to Early Treatment Diabetic Retinopathy Study ( ETDRS ) . Fluorescein angiograms were recorded from the left oculus by video fluorescent dye angiography. Retinal blood flow decreased 33 % in patients with mild retinopathy compared with control patients ( P = .001 ) and increased consecutive in more advanced phases of retinopathy, with a strong correlativity between retinal blood flow and retinopathy degree ( r2 = 0.434, P = .001 )
The addition in entire retinal perfusion during pre-proliferative retinopathy likely arises from inspissating of the capillary cellar membrane taking to occlusive angiopathy and tissue hypoxia that increases bulk blood flow demands. ( 13 ) ( 14 ) There is besides considerable grounds that the retinal autoregulatory capacity for hyperoxic vasoconstriction is blunted in diabetic topics ( 15,16 )
Grunwald et Al ( 15 ) showed in a survey utilizing LASER Doppler Velocimetry, ( n=77 ) that 100 % O external respiration reduced bulk retinal blood flow by 61 % in normal eyes, entire flow fell merely 53 % in diabetic eyes without retinopathy, 38 % in eyes with background retinopathy, and merely 24 % in eyes with proliferative retinopathy. This loss of the normal autoregulatory response to elevated PO2 suggests that the capacity to cut down bulk retinal flow in response to increased O bringing, as mediated chiefly through the actions ET-1 on pericytes is increasingly extinguished as the disease progresss. ( 16 )
Rassam et Al ( 17 ) studied the consequence of high blood pressure on retinal haemodynamics and the autoregulatory capacity of the retinal circulation under conditions of normoglycaemia and hyperglycemia. Retinal blood flow was measured before and after raising the systemic blood force per unit area in 10 normal control topics, 10 diabetic topics with blood glucose & A ; lt ; 10 mmol 11 and 10 diabetic topics with blood glucose & A ; gt ; 15 mmol/l ‘ . Laser Doppler velocimetry was used. Consequences showed that with a 40 % addition in average arterial blood force per unit area ( MAP ) , there was a important addition in retinal blood flow of 32.9 + 7-1 % in non-diabetic controls. In diabetics at the low blood glucose degree, the addition in retinal blood flow was important at 30 % addition in MAP ( 23.6 + 87 % , P = 0-032 ) and at 40 % addition ( 49-9 + 12-03 % , P = 0-004 ) . Diabetics with high blood glucose failed to autoregulate at any of the increased degrees of MAP ( 15 % addition, 27 0 + 11 1 % ; 30 % addition, 66.9 + 19.8 % ; and 40 % addition, 101 9 + 21 4 % ; P & A ; lt ; 0.022 ) . The coefficients of autoregulation showed that in non-diabetic controls, retinal vascular autoregulation broke down with additions in MAP of between 30 and 40 % . In diabetic topics, it broke down between 15 and 30 % in normoglycaemia and at less than 15 % in hyperglycemia. They hypothesised that there was an damage in retinal vascular autoregulation in response to raised systemic blood force per unit area in diabetic topics, more so at an elevated blood glucose degree.
Schemetter et Al. ( 18 ) showed that the beta-adrenergic sensitiveness of the optic vass of diabetic patients is lower than that of control topics. LASER interoferometry was used. ( 18 ) The eyes ( n = 214 ) were divided into four groups harmonizing to the modified Airlie House categorization. Fundus pulsing amplitudes were significantly smaller in group 4 than in the control group ( P & A ; lt ; 0.027 ) Local fundus pulsings in the sunspot are reduced in proliferative diabetic retinopathy, which is compatible with old findings of decreased choroidal blood flow in late phases of the disease.
Evans et Al. ( 19 ) studied 11 patients with early diabetes with minimum or no retinopathy and 11 healthy controls were evaluated for retrobulbar blood flow speed utilizing color Doppler imagination for the ophthalmic and cardinal retinal arterias. Patients and topics were tested while take a breathing room air and once more under conditions of hyperoxia. They found that hyperoxia induced a important alteration in the cardinal retinal arteria terminal diastolic speed ( EDV ) ( p = 0.008 ) and opposition index ( RI ) ( p = 0.032 ) in normal topics, but non in diabetic patients. Consequently, during hyperoxia, the diabetic patients were significantly higher for EDV ( p = 0.006 ) and significantly lower for RI ( p = 0.002 ) compared with normal controls. They concluded that hyperoxia significantly reduces cardinal retinal arteria terminal diastolic speed and significantly increases the opposition index in healthy but non in diabetic topics. ( 19 )
Patel et Al. ( 20 ) 24 non-diabetic controls and 76 diabetic topics were studied Of the diabetic topics, 12 had no diabetic retinopathy, 27 had background retinopathy, 13 had pre-proliferative retinopathy, 12 had proliferative retinopathy, and 12 had had pan-retinal photocoagulation for proliferative retinopathyIn comparing with non-diabetic controls ( 9.52 microliters/min ) and diabetic patients with no diabetic retinopathy ( 9.12 microliters/min ) retinal blood flow was significantly increased in all classs of untreated diabetic retinopathy ( background 12.13 microliters/min, pre-proliferative 15.27 microliters/min, proliferative 13.88 microliters/min ) . They concluded that retinal blood flow is significantly increased in diabetic retinopathy in comparing with non-diabetic controls and diabetic topics with no retinopathy.
Mendivil et Al. ( 21 ) compared 25 eyes of 25 patients with proliferative diabetic retinopathy before and 6 months and 1 twelvemonth after panretinal photocoagulation with a matched control group of 30 eyes of 30 healthy voluntaries. The ophthalmic arteria, short buttocks ciliary arteria, cardinal retinal vass, and vortex venas of all patients were examined, and the systolic, diastolic, and average arterial speeds were measured. Panretinal photocoagulation was performed with these parametric quantities: 800-1000 musca volitanss, 0.1 second, 500 mW. The blood speed was significantly lower in diabetic patients than in conventions in the ophthalmic arteria and the cardinal retinal arteria. After intervention, blood-flow speeds were significantly lower than before photocoagulation in the ophthalmic arteria, the cardinal retinal arteria and the cardinal retinal vena. Eyess with proliferative diabetic retinopathy showed lower optic perfusion speeds than conventions in the ophthalmic arteria and the cardinal retinal arteria. Photocoagulation resulted in a decrease in optic blood-flow speeds in the ophthalmic arteria, the cardinal retinal arteria and the cardinal retinal vena ; these values did non alter significantly during 1 twelvemonth of followup
Feke et Al. ( 22 ) used optical maser Doppler technique and monochromatic fundus picture taking to mensurate retinal circulatory parametric quantities in 39 patients with type 1 diabetes with continuance of diabetes between 7 and 20 old ages and 13 age-matched controls without diabetes. Blood force per unit area, intraocular force per unit area, and bosom rate were measured in all topics. Glycosylated haemoglobin was measured in the patients. Retinopathy was assessed utilizing standardised colour fundus picture taking and fluorescent dye angiography. They concluded that the retinal circulation of patients with type 1 diabetes with no retinopathy or background retinopathy is characterized by dilated major arterias with decreased blood velocities.
Effectss of diabetes on retrobulbar blood flow:
As the retina is supplied by the cardinal retinal arteria, we would anticipate some alterations in the cardinal retinal arteria hemodynamics in patients with diabetes. Guven et Al. ( 23 ) showed in 73 eyes in 37 patients with diabetes that the CRA maximal blood flow speed degrees were significantly higher in the pre-retinopathy group ( 9.8 +/- 2.1 cm/second ) than in the non-PDR group ( 8.1 +/- 2.2 cm/second ) . Color Doppler imagination was used to quantitate peak systolic blood flow speeds of the cardinal retinal arteria ( CRA ) . ( n=37 ) In add-on, the CRV maximal blood flow speed degrees were significantly higher in the pre-retinopathy group ( 5.7 +/- 0.9 cm/second ) than in both the PDR group ( 4.8 +/- 1.5 cm/second ) and the PRP group ( 4.9 +/- 1.7 cm/second )
Goebel et Al. ( 24 ) , utilizing colour Doppler imagination, studied 61 eyes with proliferative, 59 eyes with nonproliferative, and 26 eyes with preproliferative diabetic fundus alterations with a matched control group of 70 patients without diabetes ( 128 eyes ) . He showed that proliferative retinopathy strongly correlated with decreased flow speeds in the retrobulbar vass, chiefly the cardinal retinal arteria. These findings merely tell us that there is alteration in the retrobulbar blood flow. Whether these alterations in the retrobulbar circulation are partially a cause of retinopathy or an consequence of dysfunctional autoregulation is non clear.
Choroidal alterations in Diabetes- Diabetic choroidopathy:
Increased tortuousness, focal vascular distensions and narrowings, vascular cringles and microaneurysm formation, dropout of choriocapillaries and sinus-like construction formation between choroidal lobules in the equatorial country have been documented in the choroidal vasculature of Diabetic retinopathy patients. High declaration histological analysis of the human choroidal vasculature revealed countries of capillary dropouts, beaded capillaries, and neovascularisation. Fluorescein angiography showed delayed choroidal perfusion, and electroretinograms with unnatural oscillatory potencies in the same diabetic patients. ( 25 )
Analyzing the association between the presence of unnatural choroidal lesions evident on ICG angiography and several hazard factors, one survey found that some of the hazard factors for developing choroidopathy were the badness if diabetic retinopathy, grade of diabetic control and tightness of diabetic intervention regimen. ( 26 )
Surveies on choroidal blood flow:
Upto 80 % of the aerophilic metamorphosis of the retina is supplied by the choroid. ( 5 ) ( Retinal blood flow represents merely approximately 4 per centum of entire optic blood flow. The choroidal blood flow on the other manus ranges from 500 to 2000 ml/min/100g tissue. The mechanisms commanding optic blood flow are of different types: systemic, local, nervous, endocrinal, paracrine. Not all operate in the assorted beds. Since the retinal and choroidal arteriolas do non possess sphincters, blood flow in these tissues is merely a map of the muscular tonicity of the arteriolas and possible the province of contraction of the pericytes. Vessels tonicity is modulated by the interacted of multiple control mechanisms: myogenic, metabolic, neurogenic, and humoral, which are mediated by the release of vasoactive molecules by the vascular endothelium or by the glial cells environing the vass.
We know that there is retinal autonomic dysregulation in diabetic retinopathy. We besides know that the choroid is regulated by the autonomic nervous system. What has non been studied to a great extent though is whether there is any autonomic dysregulation of the choroidal blood flow in Diabetic patients. ( 9 ) In normal persons, the choroid has a additive relationship with the pulsation pressures. This indicates a deficiency of autoregulation capacity of the choroid in response to increased pulsation force per unit areas. In the choroid, an addition in arterial force per unit areas causes the sympathetic nervous system to increase the peripheral opposition. ( 5 )
Due to the recent progress in tools to mensurate choroidal blood flow, a great trade has been learnt about how the blood flow within the oculus occurs and how it changes with assorted emphasiss in the organic structure. POBF and OPA are indirect indexs of choroidal blood flow can be measured by techniques like optical maser interferometry, colour Doppler imagination, laser Doppler flowmetry and pneumotonometry.
Polska et Al ( 23 ) found these assorted techniques consistent in healthy persons. Laser interferometry assesses fundus pulsing amplitude. Colour Doppler imaging buttockss blood speeds in the ophthalmic and posterior ciliary arterias. Laser Doppler flowmetry assesses choroidal blood flow, volume, and speed utilizing fundus camera.
Pulsatile optic blood flow ( POBF ) can be measured with the pneumotonometer OBF ( optic blood flow ) system. ( 28 ) By agencies of a pneumatic applanation tonometer, the system assesses alterations in IOP that are caused by the rhythmic filling of the intraocular vass. The maximal IOP alteration during the cardiac rhythm is called pulse amplitude ( PA ) . Based on a theoretical oculus theoretical account, the POBF is calculated from the IOP fluctuation over clip. This hydrodynamic theoretical account is based on the premise that venous escape from the oculus is nonpulsatile. Furthermore, the optic rigidness, which is used to deduce optic volume alterations from alterations in IOP, is assumed to be equal in all topics. The computation of POBF is automatically derived from the five pulsations that are closest to each other in IOP beat-to-beat fluctuation. ( 28 )
Surveies on POBF:
Savage et Al. ( 29 ) conducted a survey utilizing the Langham pneumotonometry on patients with Non Proliferative Diabetic retinopathy. 77 diabetic topics, including 13 with mild or no retinopathy, 36 with moderate to severe retinopathy, and 28 with proliferative diabetic retinopathy ( PDR ) , antecedently treated with pan retinal photocoagulation ( PRP ) were selected. 56 non-diabetic control subjects served as the comparing group. Patients with moderate to severe non-proliferative diabetic retinopathy ( NPDR ) had POBF 18 % higher than the control ( average OBF, 943 L/min ) . Among PRP-treated topics with PDR, optic blood flow was 22 % below the control ( average OBF, 619 L/min ) , and 34 % less than chair to severe non-proliferative diabetic retinopathy. Diabetic patients with no retinopathy or mild NPDR had OBF identical from the control ( 785 vs. 797 L/min ) . Differences between the four groups were statistically important by ANOVA ( P & A ; lt ; 0.0001 ) . He showed that POBF is unaffected early in diabetic retinopathy, but increases significantly in eyes with moderate to severe NPDR. POBF is decreased in eyes with laser-treated PDR. ( 29 )
McKinnon et Al, ( 30 ) utilizing an altered pneumotonometer attached to a slit lamp, studied 82 age-matched topics divided into 4 groups: non-diabetic controls ( n = 22 ) ; diabetics with no clinical retinopathy ( n = 20 ) ; background diabetic retinopathy ( n = 20 ) ; pre-proliferative /proliferative diabetic retinopathy ( n = 20 ) . The mean pulsatile optic blood flow values were found to be increased in all classs of diabetic retinopathy ( no retinopathy 818 l/min, background 1015 l/min, pre-proliferative/proliferative 1097 l/min ) compared to the control group ( 644 l/min ) . These pulsatile optic blood flow values were significantly higher ( p & A ; lt ; 0.05 ) in tbe background and pre-proliferative /proliferative retinopathy groups compared to controls. They found that the pulsatile optic blood flow was found to be higher in diabetics compared to controls and appears to increase as the badness of retinopathy advancements. ( 30 )
Dimitrova et Al. ( 31 ) studied choroidal circulatory alterations in diabetic patients with and without background diabetic retinopathy ( BDR ) by mensurating the retro bulbar circulation with color Doppler imagination ( CDI ) . End-diastolic speed ( EDV ) in the posterior ciliary arteria ( PCA ) was decreased ( 2.55 0.80 cm/s ) and electric resistance index ( RI ) in the PCA was increased ( 0.70 0.08 ) in BDR patients compared with the control patients ‘ EDV ( 3.23 1.08 cm/s, P = 0.01 ) and RI ( 0.62 0.06, P = 0.0003 ) . RI in the CRA was significantly higher in the BDR group ( 0.74 0.09 ) than in the control group ( 0.68 0.08, P = 0.006 ) . RI in the OA was significantly higher in the BDR group ( 0.87 0.06 ) compared both with the NDR group ( 0.83 0.07 ) and with the control group ( 0.81 0.06 ; P = 0.007, P = 0.004 ) . NDR patients had a significantly higher RI in the PCA ( 0.67 0.08 ) than control patients ( 0.62 0.06, P = 0.01, while the CRA RI ( 0.71 0.09 ) did non demo important differences from the control group ( 0.69 0.08, P = 0.32 ) . Decreased EDV in the CRA was detected in NDR patients ( 2.16 0.76 cm/s ) compared with the controls ( 2.72 0.92 cm/s, P = 0.007 ) . They concluded that choroidal circulation is affected in NDR and BDR patients.
Langham et Al. ( 32 ) found that choroidal blood flow decreases with the badness of the retinopathy in diabetes due to increased vascular opposition and a reduced optic perfusion force per unit area. In a group of 19 healthy voluntaries the average ophthalmic arterial force per unit area and the optic pulsatile blood flow were calculated.
Nagoka et Al ( 33 ) used Laser Doppler flowmetry to find the Choroidal blood flow in the foveal part in 70 patients with type 2 diabetes and 36 age and sex matched healthy topics ( command group ) . 33 patients with no diabetic retinopathy ( NDR ) , 20 patients with non-proliferative diabetic retinopathy and no macular hydrops ( NPDR-MO ) and 17 patients with non-proliferative diabetic retinopathy and macular hydrops ( NPDR +MO ) . Optical coherency imaging was besides used to mensurate the foveal thickness. The group averaged choroidal blood flow values were 13.5 ( 4.9 ) , 9.4 ( 2.5 ) , 10.8 ( 4.8 ) , and 5.6 ( 2.0 ) ( arbitrary units ) in the control, NDR, NPDR/MO- , and NPDR/MO+ groups, severally. The group averaged CBF values in the NDR group decreased ( 30.2 % ; p & A ; lt ; 0.01 ) compared with the control group. The mean CBF value in the NPDR/MO+ group was besides significantly lower ( 48.2 % ; p & A ; lt ; 0.01 ) compared with that in the NPDR/MO- group. They concluded that the CBF in the foveal part significantly decreases in patients with diabetes, particularly those with macular hydrops.
LASER interferometry surveies on fundus pulsing magnitude have been done and these fail to demo any important difference in choroidal blood flow in diabetics compared to conventions. ( 18,34 ) Guven et Al. showed that flow speeds in the posterior ciliary arterias feeding the choroid are besides changed by the disease. ( 23 )
Surveies done on optic pulse amplitudes:
Schmidt et Al ( 25 ) studied OPA, utilizing the Langham optic blood flow ( OBF ) pneumotonometer system. OPA was measured in patients with insulin dependant diabetes mellitus ( IDDM ) with no ( DR-0, n = 22 ) non-proliferative ( DR-1, n = 24 ) , and proliferative ( DR-2, n = 18 ) diabetic retinopathy. He concluded that choroidal circulation remains unaffected as diabetic retinopathy progresss.
Geyer et Al. ( 35 ) studied pulse amplitude ( PA ) and pulsatile optic blood flow ( POBF ) were measured with a pneumotonometer ( OBF ) . The eyes were grouped: ( a ) normal control, n=26, ( B ) diabetes with no discernible diabetic retinopathy ( NDR ) , n=18, ( degree Celsius ) mild to chair non-proliferative diabetic retinopathy ( NPDR ) , n=20, and ( vitamin D ) really terrible pre-proliferative and proliferative diabetic retinopathy ( PPDR/PDR ) , n=12. He found that the PA and POBF values were lower than normal values in the earliest phase ( NDR ) . The POBF increased but was still below normal degrees at the NPDR phase, and so increased to an above normal degree in the PPDR/PDR phase of diabetic retinopathy. The PA was at normal degrees in these subsequently two phases. Consequences showed that there was an initial dip in the pulsatile optic blood flow during early phases of Diabetic retinopathy and so in more terrible phases, there was an addition in the pulse optic blood flow. ( 35 ) Geyer observed that the optic pulsation amplitude was lower in diabetics with no retinopathy every bit compared to normal topics and participants with documented diabetic retinopathy. They besides found that the optic blood flow increased as the patterned advance of diabetic retinopathy increased. They hypothesized that the low POBF in the non-diabetic-retinopathy patients correlated with the histological characteristics of chorio-capillaris devolution and basal lamina sedimentations. In proliferative retinopathy, they hypothesise that the choroid besides has an correspondent condition- Diabetic choroidopathy.
Geyer et Al. showed the following in their survey on OPA with the Langham OBF system
Control NDR NPDR PDR
NUMBER 26 18 20 12
PULSE AMPLITUDES 2.8 ( 1.0 ) 1.8 ( 0.7 ) 2.7 ( 0.8 ) 2.9 ( 0.9 )
Significance compared to ndr P & A ; lt ; 0.001 P=0.55 P=0.83
Pulse optic blood fow ( ul/sec ) 13.7 ( 4.5 ) 8.8 ( 3.4 ) 11.7 ( 2.1 ) 18.3 ( 3.8 )
Significance compared to command P & A ; lt ; 0.001 P=0.054 P=0.003
The above mentioned surveies of on OPA, the OPA has been measured utilizing the pneumotonometer. Dynamic contour tonometer ( DCT ) , a comparatively newer instrument used to mensurate IOP can be besides be used to mensurate OPA ( more inside informations elaborated subsequently ) . To day of the month there are no surveies of OPA in diabetics as measured by DCT.
Factors impacting optic blood flow
Consequence of Pan Retinal Photocoagulation on optic blood flow:
Pan retinal photocoagulation reduces both retinal and ex post facto bulbar blood flow. Blood flow in the ophthalmic arteria and the cardinal retinal arteria and vena are reduced for at least 2 old ages after photocoagulation therapy. Photocoagulation therapy may besides impact choroidal perfusion since devastation of the choriocapillaris reduces the amplitude of optic force per unit area pulsings. ( 20 ) ( 21 ) ( 29 ) ( 36 ) ( 37 )
Consequence of age on optic blood flow:
The blood flow into the oculus decreases with age. ( 38 ) Besides, the pulse optic blood flow decreases as the intraocular force per unit areas addition. ( 38 ) Having said that, in primary unfastened angle glaucoma, the pulse optic blood flow was shown to diminish. ( 39 )
Consequence of gender on pulsatile optic blood flow:
Gekkieva et Al. ( 40 ) observed in their survey comparing the optic pulsation amplitudes and optic blood flow in work forces and adult females. They found significantly increased POBF ( 722.6 152.8 in females versus 647.8 1164.9 in males p=0.056 ) and OPA ( 2.3 0.7 in females versus 2.0 0.6 millimeter Hg in males ) in females as compared to males.
Ocular Blood flow and High blood pressure:
Blood force per unit areas do non look to impact the optic pulse amplitude. ( 41 ) ( 42 ) These surveies were done among normal topics. They hypothesized that this deficiency of important alteration in OPAs were due to the regulative mechanisms of the baroreceptors in the carotid system before blood reached the choroidal circulation. ( 41 ) Besides, in another survey, POBF was found to be lower in diabetics without high blood pressure compared to the controls. Such a presence of systemic high blood pressure may increase the choroidal blood flow in diabetics. ( 43 )
Ocular blood flow and pulse amplitude surveies in India:
The Ocular pulsation amplitude has non been studied extensively within the Indian population. In New Delhi, Agarwal et Al. found that the pulse optic blood flow in normal Indian persons was higher than that of the Caucasic population ( 7 ) 95 normal topics were selected. 41 males and 54 females. The pneumotonometer OBF system was used for all the measurings. The average pulse amplitude obtained among the normal topics was 3.41.46 mm Hg.
There is no published informations on the normal scope of optic pulse amplitudes among the Indian subcontinent, nor any on the optic pulsation amplitudes of diabetic patients utilizing the Dynamic Contour Tonometer. With this survey we aim to document the above in the context of the Indian subcontinent.
Ocular pulsation amplitudes in Glaucoma:
The fluctuations of OPA in glaucoma has been good studied. Most surveies show that there is a decrease in the optic pulsation amplitudes in patients with primary unfastened angle glaucoma. ( 44 )
In normal eyes in which the intraocular force per unit areas were automatically raised, with the rise in Intraocular force per unit areas, the optic pulsation amplitudes addition. There is a direct relationship between the optic pulsation amplitudes and the optic rigidness. ( 45 )
Relationship of optic pulsation amplitudes and axial length:
Similarly, the fluctuations of OPA in normal topics have shown that OPA varies with the axial length of the oculus. ( 46 ) ( 47 ) Kaufmann showed a negative correlativity between OPA and axial length ( 0.27 millimeter Hg/1 millimeter of length ; P & A ; lt ; .001 ) ( 48 )
Ocular pulsation amplitudes in Retinitis Pigmentosa patients:
OPA steps by the optic blood flow system showed a important lessening in the OPA with increasing badness of Retinitis Pigmentosa. ( 49 ) The survey was done to see if there was a lessening in choroidal perfusion in patients with increasing badness of Retinitis Pigmentosa. Therefore, in the conducted survey, patients with Retinitis Pigmentosa were non selected to be enrolled in the survey.
Ocular pulse amplitude in patients with age related macular devolution:
In early ARMD, there is an addition in the choroidal blood flow, and in progressing badness of age related macular devolution, there is a decrease in the choroidal blood flow and volume. ( 34 )
Mori et Al. ( 50 ) in their work showed that the POBF and PA in the patients with exudative AMD are lower than in the patients with non-exudative AMD and normal topics. They recruited 10 patients with non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. The significance of difference in pulse amplitudes between the exudative AMD group ( PA=1.2 mm Hg ) and non-exudative AMD ( PA=2.2mm Hg ) was p= 0.04. Similarly, the significance of difference between the exudative AMD group and the controls ( PA= 2.0mm Hg ) was p=0.01. They concluded that decreased choroidal blood flow may hold a function in the development of choroidal neovascularisation in AMD.
Ciulla et Al. ( 51 ) analysed 25 topics with non exudative age- related macular devolution and compared them with 25 age-matched control topics in surveies of flow speeds in several retro bulbar vass. Colour Doppler imagination was done in his survey which showed that topics with non-exudative age-related macular devolution showed a consistent tendency toward lower extremum systolic and end-diastolic speeds in the posterior ciliary arterias. They hypothesises that the decreased extremum systolic speed, and decreased terminal diastolic speed, is consistent with decreased majority flow within these vass, likely proposing that choroidal perfusion is unnatural in non-exudative age-related macular devolution.
Dynamic Contour Tonometry:
Dynamic contour tonometry ( DCT ) is a new non-invasive technique of look intoing the intraocular force per unit area. It besides at the same time measures the optic pulse amplitude of the oculus being studied. Ocular blood flow varies with systole and diastole. This pulsatile optic blood flow ( POBF ) shows a extremum during systole. The difference in the lower limit and maximal values of the pulsatile wave contour during systole and diastole gives us the optic pulsation amplitude ( OPA ) . The OPA is an indirect index of the choroidal perfusion. ( 42 ) ( 52 )
The Pascal DCT is one such device which can be installed into the optical axis of a slit lamp. The tonometer caput piece consists of a cylindrical caput with a surface contour which comes into contact with the corneal surface and becomes equal to the contour of the cornea when the force per unit areas on both sides are equalized. The sensitive portion of the caput is merely 0.25mm2. The Pascal package measures the intraocular force per unit area and its fluctuation with every bosom beat- the optic pulse amplitude. The values are shown on an LCD show. The signals are stored in a computing machine via a wireless unit and the consequences are therefore displayed and stored for farther informations analysis.
The intraocular force per unit areas measured by the PASCAL dynamic contour tonometer are more accurate than the Goldmann applanation tonometer. The intra perceiver and inter perceiver variableness was about 0.65 and 0.44 for the DCT and 1.11 and 2.38 millimeters Hg for the Goldmann applanation tonometer. This truth of the DCT can be accounted by the fact that the readings are electronic. ( 53 ) They besides found that with DCT, the intraocular force per unit areas reduced from the first to sixth readings. This is due to the perennial force per unit area over the oculus as the readings are taken. Similarly, we suspect that there may be alterations in the optic pulsation amplitudes of patients when repeated readings are taken, therefore an norm of 3 readings are taken, with quality index 1 or 2. ( 54 )
Surveies utilizing dynamic contour tonometer:
Kaufmann et Al ( 48 ) found a average value of 3.0mmHg among the 223 eyes studied. The OPA readings ranged from 0.9 to 7.2 millimeters Hg ( average, 3.0 millimeter Hg ; 1.8-4.3 millimeter Hg ) . He found that the OPA readings were non affected by cardinal corneal thickness ( P = .08 ) , corneal curvature ( P = .47 ) , anterior chamber deepness ( P = .80 ) , age ( P = .60 ) , or sex ( P = .73 ) . There was a positive correlativity between OPA and intraocular force per unit area ( 0.12 millimeter Hg/1 mm Hg of intraocular force per unit area ; P & A ; lt ; .001 ) and a negative correlativity between OPA and axial length ( 0.27 millimeter Hg/1 millimeter of length ; P & A ; lt ; .001 )
Hoffmann et al described a average SD OPA value of 3.08 0.92 mmHg. ( 55 ) a sum of 19 eyes were examined by DCT. The survey was conducted in Germany..
Pourjavan et Al ( 42 ) , transporting out a prospective survey including 52 eyes of 28 normal topics with Goldmann applanation tonometry ( GAT ) IOPs & A ; lt ; 22 mmHg found a average OPA was 2.2 +/- 0.7 mmHg ( scope: 1-3.4 mmHg ) . The average amplitude of diurnal OPA fluctuations was 0.4 mmHg. There was no important difference in the average OPA values at each clip of the diurnal curve. Neither blood force per unit area nor age had a important bearing on the readings of OPA. OPA values of both eyes of the same single were extremely correlated ( r = 0.89, P & A ; lt ; 0.0001 ) .
To day of the month there are no surveies of OPA in diabetics as measured by DCT- . We conducted this survey to look at the OPA in changing classs of diabetic retinopathy and if presence of high blood pressure could impact the OPA in these patients.
Materials and Methods:
Study Design: experimental survey
1 ) Patients diagnosed to hold diabetes in the Medicine/ endocrinology section of CMCH and referred to the Department of Ophthalmology, CMCH for rating for diabetic retinopathy.
2 ) Known diabetics and are set abouting intervention in the Department of Ophthalmology, CMC Vellore.
3 ) Patients who are non known diabetes who presented either to our outpatient installation or cantonment installation were screened for diabetes and were included in the diabetic/ no diabetic group as per the blood consequences ( the inclusion standard as given below ) .
Institutional Review Board clearance: The survey was cleared by the institutional moralss and research commission of the Christian Medical College, Vellore. Ref. No: ( appendix1 )
Location: Department of Ophthalmology, CMC Vellore.
Patients were enrolled into the survey if they belong to the undermentioned standards:
1. For group 1 ( No DM ) , patients had no history of Diabetes or holding taken medicines for Diabetes in the yesteryear. TO confirm absence of Diabetes Mellitus, based on the American Diabetic Association guidelines for Diabetes diagnosing 2011 ( 49 ) . HbA1C degrees were done for all patients that were enrolled for the survey ( HbA1C of more than equal to 6.5 mg/dl were diagnosed as diabetics ) . Therefore, All patients with A1C degrees of & A ; lt ; 6.5 milligram /dl were selected under this group
2. For group 2 ( DM with no DR ) , they required one of the undermentioned standards before being enrolled into the survey:
a. Chronic history of Diabetes, on unwritten hypoglycaemic medicines
B. Recently diagnosed Diabetics ( based on ADA guidelines )
3. For group3 ( DM with DR ) , they required presence of diabetic retinopathy to be enrolled in to the survey.
High blood pressure was diagnosed based on the Joint National Committee – 7 study as patients who had blood force per unit area readings of more than equal to 140/90 millimeters Hg in two or more readings* .
1. Active retinal pathology other than diabetic or hypertensive retinopathy
2. Any intraocular surgery in the past 1 twelvemonth in the oculus chosen to be examined
3. No clear position to the fundus
4. History of cerebro-vascular event
5. History of connective tissue upsets and haematological upsets
6. Patients with proved glaucoma
7. Ocular hypertensives ( those with corrected intraocular force per unit areas more than 24mm Hg )
8. Leery phonograph record ( implicative of glaucoma )
9. History of any chronic topical optic medicines being used.
10. Corneal disease which prevents DCT measuring.
In add-on, presence of HbA1C & A ; gt ; 6.5 mg/dl was an exclusion standard for group 1 ( No DM )
Participants who consented to take portion in the survey were divided into 3 sub-groups based on their clinical presentation: No diabetes ( No DM group ) , Diabetics with no retinopathy ( DM with no DR group ) , Diabetics with retinopathy ( DM with DR group ) . For each patient, the right oculus was chosen by default unless the right oculus had a contraindication for the same.
Patients without Diabetes ( No DM ) were largely in-patients who were planned on being operated for cataract surgery the undermentioned twenty-four hours. For all patients without Diabetes, blood was sent for serum HbA1C degrees on the same twenty-four hours, irrespective of whether an AC/PC was done in the recent yesteryear. Blood samples were taken in the ward for the admitted patients by trained nursing staff or by the primary research worker. For the few patients who were selected with consent from the outpatient section, blood was withdrawn at the research lab in the Eye Hospital, CMC Vellore. All the blood samples were tested in the Biochemistry Laboratory under the Department of Biochemistry, CMC Hospital Vellore. Funding for the blood trial was by the research fund. A/c no 22X873 ( appendix ) Patients who were found to hold HbA1C degrees above 6.5 were discontinued from the survey.
Patients with Diabetes, with or without retinopathy were approached through the out-patient section in the Eye Hospital, CMC Vellore.
Diabetic patients ( with or without Diabetic retinopathy ) were identified by physicians in the outpatient section and referred to the chief research worker for farther rating after pointing each patient briefly on what the survey involved.
The patients were so explained in item about what the survey involved, the minimum hazards involved, and the possible benefits from the survey. If they were willing for the same, they were recruited.
Having given consent for engagement in the survey, the participants once more underwent a dilated fundus scrutiny by the rule research worker ( Dr. Ashish Kuruvilla ) utilizing a 90 D distilling lens assisted by a Haag Streit slit lamp in order to corroborate absence of exclusion standards. This besides enabled uniformity in the protocol in look intoing optic pulsation amplitudes after distension, as there are possible effects of mydriatics on the autonomic ordinance of blood flow within the oculus.
Patients with Diabetic retinopathy were classified based on the modified Airlee presenting standard exposure into mild, moderate, terrible and really terrible non proliferative diabetic retinopathy and proliferative diabetic retinopathy.
Based on the clinical findings, patients underwent OCT and FFA where indicated based on the protocol followed in the section of Ophthalmology, CMC Vellore.
Once all the exclusion standards were eliminated, the patients underwent blood force per unit area measurings by trained staff in the section of Ophthalmology. Blood force per unit areas were checked in the sitting place, after 10 proceedingss of waiting, in the right arm, except in those who had a contraindication for the same. The BP turnup and the sphygmomanometer were placed about at the degree of the bosom. If the blood force per unit areas were recorded to be more than equal to 140/90 millimeter Hg, they were rechecked after an hr. If the blood force per unit areas were still more than 140/90 mm Hg, the patients were either referred to section of Medicine, CMC Vellore ( if low-cost ) or the Low Cost Effective Care Unit CMC Vellore, for farther direction.
Once all the exclusion standards were eliminated, patients underwent Ocular Pulse Amplitude measurings utilizing the PASCAL Dynamic Contour Tonometer after come ining preliminary information about the patient on the proforma sheet. ( appendix2 )
Once the PASCAL DCT unit was attached to the Haag Streit slit lamp, a bead of topical paracaine 1 % was instilled. Having confirmed that the patient was comfortably seated and non striving to put his or her mentum on the mentum remainder, the caput was kept tilting on the caput remainder. The sensor tip of the DCT unit was so brought near to the cornea, with the patient repairing on a mark consecutive in front with the left oculus. A darkened country in the Centre of the detector tip screen ( about half of the diameter of the envisioned detector tip country ) represented the country in contact with the oculus. Visualisation was with the left oculus piece, utilizing the right oculus of the perceiver. Three values of either quality score 1 or 2 were taken and entered in the proforma ( appendix 2 ) . Intraocular force per unit areas ( which were automatically displayed on the screen along with the Ocular Pulse Amplitude values ) were besides noted down to corroborate absence of optic high blood pressure, which has been hypothesised to impact the pulsation optic blood flow and hence the optic pulse amplitude.
The measured information was so transferred to a devoted computing machine via a bluish tooth device.
All the optic pulse amplitude readings were taken by the chief research worker.
Contact inside informations were non obtained for all patients as they did non necessitate follow up visits. As all the patients examined had a CMC infirmary figure, the Patients who were found to be Diabetic based on HbA1C degrees were advised to acquire an OPD cheque up in the Low Care Effective Care Unit/ section of general medical specialty or Endocrinology, Christian Medical College Hospital Vellore.
Each proforma was stored in a file for future mention with day of the month. Age and sex were documented along with the day of the month of proving. History of Hypertension and whether on medicines was besides noted. The inside informations of medicines which the patients was on was besides noted as some antihypertensives had a intraocular force per unit area take downing consequence and therefore may hold had an consequence on the optic pulse amplitude.
Sample size computation:
Based on consequences of Orna- Geyer et Al, ( 35 ) on optic blood flow and optic pulsation amplitude utilizing pneumotonometry, there was a important difference in optic pulsation amplitudes between diabetics with no retinopathy and conventions. Non proliferative and proliferative retinopathy did non demo to hold any important difference from the normal mean. They found a average difference of 1.0 between the normal ( 2.8 millimeter Hg ; SD=1.0 ) and diabetics with no retinopathy ( NDR= 1.8 millimeter Hg ; SD 0.7 ) .
Taking this information, with alpha mistake of 5 % and power of 80 % , we calculated the sample size required in each subgroup and found it to be 12. We so decided to club all diabetic patients that showed some characteristics of Diabetic retinopathy into one group, diabetics with no retinopathy into another and in conclusion holding the normal as the 3rd group. 50 participants in each group would be equal to acquire accurate illations while making univariate analysis. Besides, this would guarantee that atleast 12 patients with mild, moderate, terrible non proliferative and proliferative retinopathy were in the Diabetics-with-retinopathy arm. We thought that these Numberss ( three times the needed sample size in each arm ) would be sufficient to analyze any new subgroups which we may detect during the class of the survey.
The sample size was calculated based on hypothesis proving for 2 agencies, utilizing the expression:
n= 2sp2 2 / ud2
Where sp2 = ( s12 + s22 ) / 2
S12: standard divergence in the first group
S22: standard divergence in the 2nd group
Ud2: average difference between the samples
Alpha: significance degree
In the analysis, all informations was analysed utilizing SPSS package version 20.0, along with Microsoft Excel 2010. To measure the clinical significance of each statistical inquiry asked, t-test for equality of agencies was used.
The entire figure of participants included in the survey was 172. 3 Patients, who were screened to be selected in the No DM arm, who were found to hold raised HbA1c ( & A ; gt ; 6.5 mg/dl ) were taken out of the survey and referred to Department of Medicine, CMC Vellore.
4 patients enrolled were non able to sit by the slit lamp for the period of clip required and hence the quality index was non 1 or 2 in these participants. Therefore, they were taken out of the survey.
One of the patients had a cervix complaint and automatically found it hard to put her mentum on the chin remainder on the slit lamp. Though non mentioned in the standards, she was non selected in the survey for obvious grounds.
3 patients refused to undergo blood trials to corroborate absence of Diabetes. All three were adult females. Two of them felt that they were excessively anemic for blood trials and the 3rd did non desire to be poked repeatedly after the trained nursing staff failed to acquire a vena in two efforts. Therefore, these 3 adult females were non included in the survey.
Average OPA among patients with no Diabetes or High blood pressure:
The entire figure of patients with no Diabetes group was 53. The average optic pulsation amplitudes in this group was 2.83 0.94. This represents the optic pulsation amplitudes among the normal population, with no systemic unwellnesss.
Gender-wise figure of patients:
Out of these 172, the figure of males were 83 and the figure of females were 89. All the patients were from South India. One patient was originally from West Bengal but was populating in Vellore during scrutiny.
Figure No.1 Gender distribution
Table No.1: Comparison between OPA of males and females
sex N Mean OPA SD
Male 83 2.65 0.96
Female 89 2.60 0.95
OPA in millimeter Hg.
The average OPA of work forces was 2.647 and for adult females was 2.60. It failed to demo a important difference in OPA with p=0.769.
Subgroup analysis was done comparing significance of difference between average OPA among work forces and adult females. None of the 3 sub-group analysis had any important difference. ( Table No.2 )
Table No.2: Comparison of males and females in assorted subgroups
No DM figure Mean OPA SD T-test significance ( comparing males and females )
males 29 2.630.90
females 24 3.050.94
DM NO DR ( n=66 )
Males 22 2.680.96
females 44 2.460.73
DM +DR ( n=53 )
Males 32 2.310.88
Females 21 2.871.34 0.069
Age wise distribution:
The age of patients enrolled in the survey ranged from 40 to 79 old ages. The decennary wise distribution of participants is shown in Figure 2. Majority of the patients were in the fifth decennary with about similar figure s in the 4th and 6th decennary. There were merely 5 % of participants in the 71- 80 twelvemonth age group. The graph below shows the distribution of the figure ( in absolute Numberss ) of participants in each group.
Table No. 3: Average OPAs among patients grouped by decennary
Age yrs figure Mean PA SD
40-50 48 2.631.07
51-60 71 2.600.89
62-70 45 2.620.90
71-80 8 2.841.19
average 172 2.630.95
OPA in millimeter Hg.
The average OPA was about the same in all the groups being considered. The average OPA among the 172 population considered was 2.625. We took the subgroup 71-80 and cross tabulated with the average OPA to see if the difference was important. There was no important difference seen ; p= 0.54.
Table No. 4: Significance of difference in OPA between groups based on age
Sum of Squares Df Mean Square F Sig.
Between Groups.405 220.127.116.112
Within Groups 155.413 168.925
Entire 155.817 171
ANOVA was done to see if there was any important difference between any of the bomber groups. The tabular array above shows the same. The trial failed to demo any important difference between the four groups. P=0.932
SUB GROUP ANALYSIS:
Analysis between the 3 major bomber groups:
As described in the methodological analysis, there were 3 subgroups that we had selected. Group 1 was No DM, group2 DMwith no DR, and Group 3, DM with DR. Given below is the distribution of these 3 subgroups.
Figure No. 2 Percentage of patients without DM, with DM and no DR, with DM and DR
Table No.5: Analysis between the 3 major subgroups
figure Mean OPA SD t-test ( compared to controls )
No DM 53 2.83 0.94
DM no DR 66 2.54 0.81 0.068
DM and DR 53 2.53 1.11 0.13
OPA in millimeter Hg.
Comparison of the groups DMnoDR with DM+DR:
There was no important difference between the two groups. P= 0.972.
Distribution of patients in each phase of Diabetic retinopathy:
Out of the 53 in the Diabetics with retinopathy arm, 14 were with mild non proliferative diabetic retinopathy, 18 with moderate retinopathy and 21 with terrible non proliferative and proliferative diabetic retinopathy.
Figure no.3: Distribution of patients in each phase of Diabetic retinopathy
The mean Ocular pulse amplitude among the 3 groups are as shown:
Table No.6: Average OPA of patients in assorted phases of retinopathy
Group figure Mean OPA SD t-test ( compared to controls )
No diabetes ( controls ) 53 2.83 0.94
Diabetess with no retinopathy 66 2.54 0.81
Mild NPDR 14 2.70 1.51 0.69
Moderate NPDR 18 2.66 0.93 0.50
Severe NPDR, PDR 21 2.31 0.95 0.034
OPA in millimeter Hg.
There was a important lessening in average OPA in those with terrible pre-proliferative and proliferative diabetic retinopathy.
Comparison of LASER therapy on values of OPA among terrible NPDR- PDR groups:
Out of the 21 patients with terrible non proliferative + proliferative diabetic retinopathy subgroup, 11 had had no LASER therapy and the remainder of the patients had LASER.
Table No.7: Comparison of patients with and without LASER in patietns with terrible NPDR/ PDR
Severe NPDR/PDR n Mean OPA* SD
No LASER 11 2.33 0.86
LASER 10 2.28 1.09
*OPA in millimeter Hg
High blood pressure among Non-Diabetics and Diabetics:
Though Hypertension was non an exclusion standard for choice of participants with no Diabetes, it was found that patients with Hypertension without Diabetes were really few. Besides, there were 2 patients in whom Diabetes was found on making HbA1c, both of whom claimed that they had Hypertension but no Diabetes.
The pie chart illustrates the point that the entire per centum of patients with Hypertension but no diabetes was rare.
On the other manus, out of the patients with Diabetes, 42 % had Hypertension, all of them were on medicines. The remainder of them underwent blood force per unit area cheques and were found non to be Hypertensives.
Figure no.4 Percentage of non diabetics with Hypertension
Figure no. 5 Percentage of Hypertensives among Diabetics
The OPA in the assorted classs of patients in the presence and absence of high blood pressure is depicted in table 8
Table No.8: Comparison of Hypertension among assorted subgroups:
N ( figure in each class ) Mean OPA` SD t-test analysis
No DM, No HTN 48 2.80 0.91
No DM, HTN + 5 3.14 1.18 0.44
DM, No HTN 69 2.40 0.93
DM, HTN + 50 2.73 0.96 0.06
DM, no DR, HTN+ 30 2.61 0.67
DM, no DR, no HTN 36 2.48 0.91 0.53
DM, DR+ ,
no HTN 33 2.30 0.95
DM, DR+ , HTN+ 20 2.90 1.28 0.056
OPA in millimeter Hg.
Among the diabetic patients who had retinopathy, lower OPA was found in those patients who had no high blood pressure every bit compared to those who were hypertensive. ( p= 0.05 ) . It was significantly lower OPA as compared to controls every bit good. ( p=0.02 )
Type of anti Hypertensives taken by those with High blood pressure:
Anti-Hypertensive medicines taken by these patients were besides documented. All the patients were merely on one antihypertensive. The consequences are as follows:
Table No. 9: Antihypertensive medicines
Medicines Number Percentage among Hypertensives ( % )
Beta Blockers 9 18
Calcium channel blockers 2 4
ACE inhibitors 19 38
Angiotensin Receptor blockers 1 2
thiazides 6 12
Not on therapy 13 26
The above tabular array shows a important per centum of patients who were non on intervention despite being on medicines for Diabetes and cognizing that they had Hypertension. It was beyond the range of the survey to find why these participants were non on antihypertensives despite cognizing they had Hypertension.
Figure No.6 Patients on Antihypertensive medicines in per centums
The Numberss were non equal to compare between Hypertensives with assorted antihypertensives. ANOVA done with the above information showed a significance of merely 0.159.
Table No.10: Average OPA among Hypertensives on antihypertensives
Antihypertensive used N Mean OPA SD
Beta blockers 9 2.310.46
Calcium channel blockers 4 2.160.99
ACE inhibitors 19 3.100.75
Angiotensin receptor blockers 1 3.57
Thiazides 6 2.600.88
Not on therapy 11 2.590.39
OPA in millimeter Hg
ACE inhibitors trended to demo increased optic pulsation amplitudes as compared to the other antihypertensives used.
Assorted optic perfusion abnormalcies at micro and macrovascular degrees every bit good as defects in autoregulation occur in diabetics. Changes in the retinal capillary endothelium and pericytes, doing assorted manifestations of diabetic retinopathy have been good established. Choroidal alterations have besides been documented in diabetics ( 26,4 )
Different surveies on optic blood flow and OPA have shown variable consequences. The varied consequences could be due to 1 ) the different methods used to analyze the optic blood flow. It is possible that some methods measure the flow in the smaller choroidal vass and some likely step the flow in the larger choroidal vass. 2 ) The fact that the POBF could change with the continuance of diabetes, ( ref Kono et al 1996 iovs ) with diabetics of shorter continuance holding higher POBF as compared to those with longer continuance of diabetes ( ref Kono ) . This could explicate the varied consequences of POBF in the class of patients with DM but no DR with some surveies demoing no alteration ( 49 ) and other surveies demoing reduced blood flow ( 32,35 ) . 3 ) Acute accent alterations in the blood sugar degrees can take to varied optic blood flow. Bursell et Al found that acute hyperglycaemia resulted in increased retinal blood flow in diabetics with no retinopathy. ( 57 ) 4 ) Most surveies of optic blood flow and OPA in diabetics have non looked at the confusing consequence of co-existing high blood pressure. Hypertension causes increased retinal perfusion force per unit area every bit good as altered choroidal perfusion. Whether this will ensue in increased OBF will depend on the extent of alteration in the intraocular vass, both choroidal and retinal, every bit good as the province of the general circulation. Simple extrapolation of haemodynamic rules make it possible to speculate that increased blood force per unit area could ensue in increased tissue blood supply or, paradoxically, a reduced blood supply when the vass