Insulin production and its
Despite the success of Banting in isolating insulin, the earliest form contained many impurities and needed to be given frequently in large quantity as much as 5-10ml intramuscularly. Severe inflammation and abscesses were common. Purification of the extract reduced the side-effects and the amount required.
     The earliest form of insulin came 
      from the pig pancreases from 
       the slaughterhouses. Eli Lily
         was the first company to
mass produce insulin.
Later on insulin was also obtained from cow pancreases. Allergy occurs
in some patients due to the presence of foreign proteins. Also for religious
reasons, animal-based insulins are 
not acceptable to some.
With the advance of genetic, recombinant DNA synthesis of human insulin is now the preferred form of insulin. 
The 15th Congress of International 
Diabetes Federation in Kobe 1994.
Insulin Crystals. Insulin is a peptide hormone and unlike steroid hormone cannot be taken orally as it is
digested by enzymes.
50th Anniversary of the Danish 
Diabetes Association. Insulin Crystals. Denmark is the biggest producer of insulin outside the USA due to the pioneering work of her Nobel prize winning scientist Kroger.
38th European Diabetes Congress
in Budapest. An insulin molecule.
A three-dimensional structure 
of insulin.
Section 8 Management of Diabetic Maculopathy
8.1 Introduction
Diabetic maculopathy (DM) causes gradual and largely irreversible loss 
of central vision. many patients with DM are elderly; thus assessment 
and treatment may be complicated by co-existing ocular pathology, 
such as cataract, glaucoma or a poor mydriasis response. Medico-social 
problems may also militate against optimal management.
Diabetic maculopathy is caused by oedema from leaking capillaries 
and/or ischaemia due to capillary loss. Diabetic changes to the choroidal 
vasculature may also worsen the ischaemia and contribute to the 
oedema by reducing retinal pigment epithelial function. Preventable 
visual loss is largely due to disruption of the fovea and perifoveal neuro-
retina by oedema. The ETDRS and the British Multi-centre Photo-
coagulation Study showed that appropriate macular photocoagulation 
was effective in preventing central visual loss due to macular oedema, 
in many cases, for up to seven years. Optimal management depends on 
detection and treatment by photocoagulation of oedema before the 
fovea is involved. The aim of treatment is to prevent further visual loss, 
since visual acuity rarely improves following treatment, best results are 
achieved by applying treatment before central vision deteriorates.
Loss of central vision due to macular ischaemia or generalized oedema 
cannot be prevented by photocoagulation. In young people visual acuity 
may be preserved despite macular ischaemia. Many cases of diabetic 
maculopathy involved co-existing macular oedema and ischaemia. In 
such cases, the prognosis depends on the extent of the oedema and 
the severity of the ischaemia. Central vision can remain surprisingly good, 
even with marked retinal capillary closure, provided coexisting oedema is 
treated before it involves the fovea.
8.2 Indications for treatment
Treatment is indicated when the maculopathy threatens the fovea or 
perifoveal area. Isolated microaneurysms around the fovea without 
clinical evidence of retinal thickening therefore do not merit treatment, 
but they should continue to be observed at regular intervals. Small 
localized areas of retinal thickening outside the central macula area 
do not require treatment, though such cases do require regular follow-up. 
Fluorescein angiographic evidence of retinal oedema in the absence of 
clinically obvious retinal thickening (Clinically Significant Macular Oedema, 
CSME in the ETDRS) is not normally regarded as an indication for 

8.3 Treatment protocols for diabetic maculopathy
The aim of treatment is resolution of retinal oedema before the fovea is 
involved. This is achieved using laser therapy to the macula. How laser 
therapy achieves this effect is unclear. There is either a direct effect on 
leaking microvascular complexes in the retinal circulation or an indirect 
effect mediated through the retinal pigment epithelium.
Safe treatment depends on accurate identification of the fovea and 
avoidance of excessively intense burns. The fovea can be difficult to 
identify if there is considerable oedema. Excessively intense burns can 
be avoided by starting treatment with very low powered burns, and 
gradually increasing the intensity until a satisfactory moderate blanching 
of the retina is achieved. Energy uptake varies, depending on the degree 
of the retinal oedema, so it is important to reduce power when treating 
less oedematous areas. 
Satisfactory results can be achieved with a number of different light 
wavelengths (see elsewhere in these guidelines). The most frequently 
used wavelengths are 514nm (the ‘Green’ component of the Argon 
Blue/Green laser) and 810nm (from the infra-red diode laser). The Argon 
blue/green laser should not be used for treatment of microaneurysms 
that are very close to the central area. This is because the blue light 
from this laser (487nm) is absorbed by xanthophylls pigment overlying 
the parafoveal area. this can cause nerve fibre layer damage and 
parafoveal scotomata (see section on lasers). 
In general, the blue laser waveband is not recommended due to its 
possible deleterious effects on the user (see Section 5.2).
8.3.1 Focal maculopathy
This type of maculopathy responds most readily to photocoagulation. 
Areas of focal leakage, usually a the centre of the exudative rings 
(identifiable if necessary by fluorescein angiography but only if doubt 
exists as to their precise location), are treated using a 50-100 micron 
beam at sufficient power level to obtain moderate blanching of the 
retina. When the microaneurysm is close to the fovea, a short 
superficial burn just sufficient to blanch it may be used.
However, the treatment of microaneurysms within 300 micron of the centre 
of the fovea should be undertaken with caution because of the significant 
risk of closure of the perifoveal arcade.
An alternative to direct treatment of focal leakage is to apply a gentle grid 
to the entire circinate ring, including the margin, in a fashion similar to that 
used for diffuse maculopathy.
Figure 26 Grid laser treatment  of diabetic maculopathy. a) Fundus 
appearance b) Areas of laser therapy seen on fluorescein angiography 
as spots of 'show-through' (arrow). Click on picture for a larger view.
8.3.2 Diffuse maculopathy
Diffuse maculopathy is a more difficult form of diabetic retinopathy to treat. 
However, grid laser photocoagulation offers the only available, validated 
therapy. The technique consists of applying 100-200 micron burns delivered 
at a power level sufficient to obtain a minimum blanching reaction the 
pigment epithelium in a grid pattern over the central macula avoiding the 
fovea itself (Figure 26a, b). Patients may visualize the grid entoptically.

8.3.3. Mixed maculopathy
Focal and diffuse areas of oedema should be identified and treated as above.
8.3.4 ischaemic maculopathy
Ischaemic maculopathy does not respond to laser therapy. However, if the 
degree of ischaemia is sufficiently large that it performs part of the pre-
proliferative retinopathy, then this of itself may warrant therapy.
8.3.5 Diffuse non-responsive macular oedema
Severe diffuse macula redeem which is non-responsive to grid laser 
photocoagulation or repeated grid laser photocoagulation, may benefit from 
vitrectomy with removal of the attached posterior hyaloid face. Cases likely 
to benefit have an appearance which may be very subtle, but presents as 
posterior hyoid face thickening, surface wrinkling and a detectable sheen, or 
abnormal reflex from the inner limiting lamina. The surgical goal should be the 
removal of all thickened posterior hyaloid and cortical gel material via a three 
port pars plana vitrectomy (see next section). Approximately 50% of patients 
may experience moderate improvement of vision, up to 2 lines or more. 
8.3.6 Diffuse maculopathy in the presence  of neovascularization
Occasionally maculopathy co-exists with disc or retinal neovascularization. 
Whether to treatment the new vessels with PRP or to treat the 
maculopathy first depends on the age of the patient and the relative 
severity of the retinopathy. In young patients with active new vessels it 
is generally recommended to treat the new vessels first with PRP since new 
vessels in these patients can advance rapidly with devastating consequences. 
In older patients with NIDDM, it is better to treat the maculopathy first or at 
least at the same time since PRP itself in these patients can hasten the 
progression of the maculopathy. Fractionating PRP into sessions of 700-800 
burns separated by 2-3 weeks reduces the risk of this progression.

8.4 Follow-up after treatment of diabetic maculopathy
Patients with diabetic maculopathy should be reviewed 3-4 months after 
treatment. If oedema persists, or if the visual acuity worsens, repeat 
fluorescein angiography may be helpful in identifying areas of residual 
focal leakage which should then be retreated. Treatment of leaking areas 
associated with exudates may cause regression of the exudates over 
many months.
Since focal maculopathy can recur, patients with treated maculopathy 
should be followed for a sufficient time to ensure that the condition is 
inactive. Patients with cataracts and treated diabetic retinopathy should 
have the maculopathy reassessed before cataract surgery since surgery 
can induce recurrence or advance of existing macular oedema. Any persistent 
areas of oedema should be re-treated either before or soon after surgery.
Epidemiology Clinical features Risk factors Screening
Lasers and lenses. NVD,, NVE.. Maculopathy
Vitrectomy. Cataract Special problems Counselling
References.. AAO guidelines Atlas of Retinopathy Contact lenses
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