Intraocular pressure variation (ocular hypertension) in diabetes mellitus

Abstract

Ocular hypertension (OHT), defined as increased intraocular pressure (IOP, > 21 mmHg) in eyes without optic disc changes or visual field changes, is a condition that puts an eye at higher risk of developing glaucomatous optic neuropathy and may be related to the translaminar pressure gradient, individual differences in IOP-related glaucoma susceptibility, effects of arterial blood pressure on the optic nerve head, and vasospastic factors. IOP remains the most common modifiable risk factor to protect eyes against the development of glaucoma. The association between OHT and diabetes mellitus (DM) is poorly understood, although ocular effects of both conditions are related to vascular compromise of retinal and optic nerve circulation. Increased IOP in diabetic patients is attributable to increased aqueous osmotic gradient and accumulation of extracellular matrix constituents in the trabecular meshwork. Autonomic dysfunction and genetic factors may also play a role. Apart from eyes without diabetic retinopathy (DR) changes, OHT can also be observed in eyes with DR, where it can develop with or without antecedent vitreoretinal intervention. For example, photocoagulation of the retina in earlier stages of proliferative DR protects against the development of OHT, whereas intraocular silicone oil injection promotes it. While IOP has been directly implicated as an independent risk factor for DR, the retinopathy in DM is also related to comorbidities, like hypertension and heart disease, that are also correlated with OHT. All these factors are discussed in a comprehensive review exploring the association of OHT and DM in detail.

Key Words: Intraocular pressure; Ocular hypertension; Hyperglycemia; Corticosteroids; Visual impairment

Core Tip: Ocular hypertension (OHT), defined as increased intraocular pressure (IOP, > 21 mmHg) in eyes without optic disc changes or visual field changes, is a condition which puts an eye at higher risk of developing glaucomatous optic neuropathy. It is one of the important concerns in diabetes mellitus (DM) even in the eyes which do not have diabetic retinopathy (DR) changes. OHT can also be observed in eyes with DR where it can develop with or without antecedent vitreoretinal intervention. While IOP has been directly implicated as an independent risk factor for DR, the retinopathy in DM is also related to comorbidities, like hypertension and heart disease that are also correlated with OHT. The understanding of the complex interplay of pathophysiologic risk factors is important for early identification and management of patients predisposed to this condition.

INTRODUCTION

The incidence of diabetes mellitus (DM) in the world is increasing. DM is now prevalent in about 8.8% of the adult population of the world, and the number of affected individuals is estimated to rise beyond 640 million by 2040. DM is primarily considered a microangiopathy, affecting cellular metabolism and vascular endothelial interactions at a sub-microscopic level, that culminates into complications like diabetic retinopathy (DR), nephropathy and neuropathy[1].

Notably, the ocular complications of DM are not limited to retinopathy alone. The disease can affect almost all the structures of the eye, and its well-known manifestations include infections of the adnexa, eyelids and ocular surface, cataracts, retinopathy, maculopathy and optic neuropathy. However, one of the rarely mentioned but clinically significant complications of DM is a rise in intraocular pressure (IOP) or ocular hypertension (OHT)[2-5].

OHT has been variously defined by different authors taking the cutoff presenting IOP as > 20 mmHg, > 21 mmHg or > 25 mmHg, the exact value still disputed. However, it is classically defined as increased IOP (> 21 mmHg) in eyes without optic disc changes or visual field changes suggestive of glaucomatous optic neuropathy[6]. It follows that an accurate measurement of IOP, stereoscopic examination of the optic discs under magnification and a standard automated perimetry are the minimum prerequisites to diagnose a case of OHT. Gonioscopy for assessment of the angle of the anterior chamber may also be considered a useful adjunct.

The prevalence of OHT in the general population ranges between 2.7%–3.8%[7]. The known factors associated with OHT are DM, systemic hypertension, and dyscholesterolemia[8]. As the patients are routinely referred to ophthalmic clinics for the detection of retinopathy in these metabolic disorders, especially DM, many of them are incidentally detected as having a high IOP and subsequently evaluated for glaucoma. OHT may be initially diagnosed in these patients by the absence of background retinal changes with a high IOP and investigations not suggestive of glaucoma. However, follow-up of such patients is equally important, as studies have showed an increase in relative risk of development of OHT during the clinical course of the disease.

The development of DR in these patients further complicates the picture in cases of OHT, as both conditions have to be taken into account while treating these patients. Vitreoretinal interventions for DR can further complicate the scenario, depending upon the type, number, duration and laterality of the intervention performed. IOP remains the most common modifiable risk factor to protect eyes against the development of glaucoma, and the therapeutic target in most approaches to cases with OHT[9].

Despite current advances in the understanding of OHT and DR as distinct entities, there are gaps in the current understanding and management of OHT in diabetic patients. Many studies appear to provide conflicting conclusions on various aspects of OHT in DR, including its influence in the latter’s onset and progression as an independent risk factor or otherwise, and it is pertinent to know the scenario behind such reports. It is also important to review the influence that interventions required for the management of DR have on IOP levels.

With this clinical background, the present review aims to provide a comprehensive impression of the intricate link between OHT and DM, leading to an understanding of the pathophysiology of IOP rise in DM, the interplay of local, systemic and iatrogenic factors, the measurement of IOP in DM for an accurate diagnosis of OHT, and further course of management in these cases.

SEARCH METHODOLOGY

A literature search was performed in PubMed and Google Scholar, encompassing the MEDLINE, Scopus and Embase databases. The search keywords included “diabetes”, “complications”, “retinopathy”, “maculopathy”, “ocular hypertension”, “intraocular pressure”, “silicone oil”, “neovascularization”, “intraocular lens”, “intravitreal injection”, “retinal laser photocoagulation”, “vitrectomy”, and “vitreoretinal surgery”. We included only those articles that were highly cited and published in the English language from 1983 to 2024. The Reference Citation Analysis Tool was utilized to assess the impact and relevance of the referenced articles. Four independent researchers reviewed 1672 manuscripts and after eliminating duplications, finalized 74 relevant articles to be included in the manuscript.

PATHOPHYSIOLOGY OF OHT

Many theories have been proposed to explain the development of OHT in DM. Anatomical, mechanical, genetic, vascular, immunological and endocrinological factors have been identified in this regard (Figure 1).

Figure 1 Pathophysiological mechanisms of ocular hypertension in diabetes. ECM: Extracellular matrix.

The translaminar pressure gradient (TLPG) is the differential of pressure between the IOP from within the eye and the cerebrospinal fluid pressure in the optic nerve sheath, equal to the intracranial pressure, expressed as per unit thickness of the lamina cribrosa[10,11]. It is hypothesized that elevated retro-laminar pressure may lead to a normal TLPG even in eyes with raised IOP[12]. This, coupled with inter-individual differences in IOP-related glaucoma susceptibility, may be responsible for maintaining the retinal nerve fibre layer and axonal homoeostasis, so that glaucomatous optic nerve damage does not ensue even after prolonged periods of IOP elevation.

These theories, however, do not account for the effects of arterial blood pressure on the optic nerve head. The ocular perfusion pressure is defined as the difference between the arterial blood pressure and the IOP in systole (systolic OPP), diastole (diastolic OPP), or when considering mean arterial pressure (MAP), in which case the OPP is given by the computing the difference between two-thirds of MAP and the mean IOP[13]. The OPP is regulated by several factors, one of which is nitric oxide which not only affects blood flow to optic nerve and retina but also produces aqueous humour and maintains IOP[14]. Nitric oxide has been recently identified as a factor responsible for maintenance of the balance between IOP and OPP, and is regulated in response to various local and systemic stimuli and is now an emerging therapeutic target in open angle glaucoma.

Adding to the mix of factors above, are the role of genetics, autoimmunity and ischemia[15]. The differences in susceptibility of the optic nerve to atrophy in response to pressure and laminar shear, as also the magnitude of elevation and diurnal variation of IOP may be controlled by yet poorly understood genetic mechanisms linked to the MYOC. PITX2, FOXC1, and CYP1B1 genes. High IOP is often related to variations in GAS7 and TMCO1 genomic regions[16]. There are about 40 genes and over 100 common variants identified through various molecular genetic approaches which can affect IOP or susceptibility to optic nerve damage in response to the same. Higher Polygenic Risk Score has been found related to amplified risk for progression to open angle glaucoma in patients with OHT[17].

Autoimmune mechanisms may exert neuroprotective features and impact the pattern of protein expression in neuroretinal cells[18]. Finally, the effect of ocular ischemia is profound not only due to alteration of the OPP, but anterior segment ischemia causing ischemia of endothelial cells of Schlemm's canal contributes to OHT[19].

INCREASED IOP IN DIABETES

The initial insights regarding the development of OHT in diabetes evolved when the landmark study of OHT and early glaucoma–the OHT study initially reported that diabetes was protective against conversion of OHT to glaucoma although the study was later found to be underpowered[20,21]. The Early Manifest Glaucoma Trial was the first large randomized, clinical trial understanding the role of IOP and the natural history of glaucoma and evaluating the rationale for glaucoma screening. High IOP was identified as one of the most important factors for the development and progression of glaucoma[22].

The association between OHT and DM is poorly understood, although ocular effects of both conditions are related to vascular compromise of retinal and optic nerve circulation. There is conflicting evidence how uncomplicated diabetes is associated with IOP rise, and whether the latter predisposes diabetic patients to develop DR and/or is associated with progression of the retinopathy (Figure 2).

Figure 2 Ocular hypertension mechanisms in diabetic retinopathy and interventions. OHT: Ocular hypertension; VEGF: Vascular endothelial growth factor

OHT in diabetes without retinopathy

Diabetic patients present with a pooled average increase in IOP of almost 0.1 mmHg for every 10 mg/dL increase in the level of fasting plasma glucose[23]. Presence of DM has been associated with an overall rise in mean IOP of both eyes of 0.31 mmHg[5].

Recent data suggest that patients with DM are 1.52 times more likely to develop OHT. In a study among diabetic subjects, 13.7% presented with an IOP above 21 mmHg[4]. However, a proportion as high as 80% of diabetic patients can have OHT at presentation even after adjusting for central corneal thickness (CCT)[24]. Matsuoka et al[25] showed a positive correlation of IOP with HbA1c levels in patients with DR, indicating that poorer control of diabetes predisposes to the development of higher IOP.

In a Romanian study, it was found that an increase in standard deviation of the diabetes duration is expected to increase the IOP by 0.52 mmHg in type 2 DM patients with HbA1c < 7% and duration of DM < 15 years[4]. Insulin has also been reported to affect IOP, with lower IOP associated with insulin-induced hypoglycemia and increased IOP associated with insulin resistance[26-28]. Diabetic persons in a population-based study in Wisconsin tended to have higher mean IOP than the nondiabetic persons. Higher blood pressure, earlier time of day of IOP measurement, absence of nuclear-sclerotic cataract and, in some comparisons, female gender, were significantly associated with higher IOP. In the age group of 13-18, OHT was prevalent in 6.6% of younger-onset and 9.3% of older-onset diabetes compared to 3.4% of controls. However, the study showed that the type of DM was not significantly associated with IOP[29].

In contrast, recent findings in the literature suggest a U-like relationship between HbA1c and IOP–very poor or very strict control of glucose levels can be associated with raised IOP. It has been proposed that a target HbA1c of 7%-7.7% reduces the occurrence of significant vascular events in type 2 DM regardless of the duration of DM[30]. Diabetic patients are also more susceptible to glaucoma as a result of IOP rise[31,32].

DM causes microvascular injury affecting the autoregulatory mechanism of retinal blood vessels and optic nerve thus leading to associated increase in IOP. Strict glycemic control could cause endothelial dysfunction, with altered ocular blood and aqueous humor flow. Hence, DM may increase the risk of glaucoma by causing the blood vessels to become more permeable, leaky, or constricted[33]. Increased IOP in patients of DM can also result from increased aqueous osmotic gradient[34]. Contrarily, hyperglycemia could also increase oxidative stress and levels of vascular endothelial growth factor, thus altering the outflow of the aqueous humor resulting in reduced IOP[35].

Increased expression of extracellular matrix (ECM) components, including fibronectin, causes increased IOP in chronic hyperglycemia. The expression of fibronectin is increased under high glucose in trabecular meshwork (TM) cells, which leads to increased TM outflow resistance[36,37]. It can be held that these changes are part of a compensatory and protective mechanism, as OHT may reduce the metabolic requirement of the retina by means of relative ischemia[29]. It has also been proposed that modifications in patterns of connective tissue remodeling in DM may affect the lamina cribrosa, thereby potentially raising the eye’s susceptibility to glaucoma through biomechanical changes at the optic nerve head[38].

OHT in diabetes with retinopathy

Apart from the eyes which do not have DR changes, OHT can be observed in eyes with DR where it can develop with or without antecedent vitreoretinal intervention. A cohort study revealed that among patients with DM, those having high IOP were more likely to develop DR within 5 years[39].

Protein kinase C (PKC) is a key player in the pathophysiology of DR, and elevated PKC may also be responsible for abnormal expression of matrix metalloprotease (MMP) in the TM. Decreased MMP levels decrease turnover of the ECM in the TM, causing impaired aqueous outflow and elevated IOP[34].

Recent research has uncovered the OHT-DR relationship at the genetic level – numerous Single Nucleotide Polymorphisms at the genome-wide significance level have been implicated to cause the interaction of OHT and DR. IOP is causally associated with DR and is a significant risk factor for it, although the odds of developing retinopathy are low. This has been found to be true even after excluding the interference of hypertension as an additional risk factor. Conversely, the results of reverse mendelian randomization analysis showed there is no causal relationship between DR and IOP[39].

OHT in nonproliferative DR

In the study by Matsuoka et al[25], IOP increased progressively with the grade of DR – the patients without retinopathy had lower IOP than those with non-proliferative retinopathy, and these patients in turn had lower IOP than those with proliferative DR (PDR)[25]. In a cohort of diabetic children, those who developed retinopathy were found to have significant elevation of their IOP (P < 0.01) compared to those without DM or without DR[40]. However, in a recent cross-sectional study, IOP change was not found to be an independent risk factor in DR progression, which is contrary to the early research findings[41]. Similarly in another study, increase in IOP did not increase risk of more severe DR[42]. OHT may, in fact, retard the development of PDR by reducing the differential between intravascular pressure of the capillaries and the pressure in the vitreous[29]. A suppressive effect of OHT on DR has been noted in various studies, and glaucoma has even been found to be responsible for asymmetry of DR[43,44].

It can thus be inferred that the interrelationship between IOP and DR development and progression is complex. It likely involves the balance between the microangiopathic effect of DM tending to raise the IOP, and the same effect being suppressed by raised IOP due to reduced metabolic demand after subclinical cellular injury.

OHT in proliferative DR

OHT can occur in PDR by the complex interplay of various interrelated mechanisms (Table 1). In the absence of any intervention, secondary narrowing of the anterior chamber angle caused by neovascularization of the angle following rubeosis iridis may cause IOP rise that may progress to intractable glaucoma in the setting of zipping angle closure[45]. IOP rise may also occur as sequelae of intervention including laser photocoagulation, anti-vascular endothelial growth factor or corticosteroid implant injection as well as after vitreoretinal surgeries. In a study, the proportion of patients of PDR affected by OHT was 37.5% and the severity of retinopathy was significantly different amongst them[43]. Thus, OHT in PDR warrants special consideration on a case-to-case basis, wherein the long-term visual prognosis depends on the condition of the retina as well as maintenance of normal IOP so that OHT does not progress to glaucomatous optic neuropathy.

Table 1 Mechanisms of development of ocular hypertension specific to proliferative diabetic retinopathy.

Intervention	Cause of IOP rise	Mechanism of OHT	Intervention1
Nil	Rubeosis iridis and neovascularization of angle	Progressive and zipping angle closure	Retinal laser photocoagulation
			Intracameral anti-VEGF injection
Retinal laser photo-coagulation	Intraocular inflammation	Acute release of cytokines in response to laser-induced tissue injury	Topical drugs: Corticosteroids, non-steroidal anti-inflammatory drugs, cycloplegics
		Ciliary body edema
Intravitreal injection	Acute rise in intraocular fluid volume after anti-VEGF injection	Vitreous pressure	Immediate anterior chamber paracentesis
		Forward movement of iris-lens diaphragm	Intravenous mannitol, oral glycerol
	Corticosteroid response	Trabecular dysfunction and aqueous outflow impedance	Topical antiglaucoma medication like aqueous suppressants
Vitreoretinal surgery	Surgical trauma	Acute inflammation	Topical drugs (as above)
		Erythroclastic response	Uveoscleral outflow stimulators
		Ciliochoroidal effusion	Topical drugs (as above), oral steroids
		Fibrinous membrane formation	Membranectomy
			Tissue plasminogen activator injection
			Laser peripheral iridotomy
	Intraocular tamponade	Silicone oil	Inferior (Ando) iridectomy
			Oil removal
		Intraocular gas expansion	Topical drugs (as above)
			Gas removal or exchange
	Corticosteroid response	As above	As above

¹Increased intraocular pressure control may be aided by antiglaucoma medication, nonpenetrating glaucoma surgery, filtering surgeries and/or placement of glaucoma drainage devices or diode laser cyclophotocoagulation as required.

VEGF: Vascular endothelial growth factor; OHT: Ocular hypertension; IOP: Increased intraocular pressure.

Historically, attempts were made to aid the treatment of PDR by photocoagulation along with artificial elevation of IOP by the use of topical corticosteroids, wherein elevations of > 12 mmHg led to significantly better protection as well as visual improvement, while > 40 mmHg caused regression of neovascularization in a minority of patients[46]. Photocoagulation of the retina in earlier stages of PDR protects against the development of OHT. However, corticosteroids can cause IOP rise warranting active intervention to prevent progression of OHT to glaucoma, so this approach is no longer in practice.

The IOP elevation after intravitreal anti-vascular endothelial growth factor injections is mostly limited owing to their clearance from the vitreous, posing no long-term effects in patients not otherwise predisposed to glaucomatous optic neuropathy[47]. These episodes of OHT are effectively controlled by topical medication as they are transient[48].

Consistent rise of IOP may be produced by intravitreal corticosteroid injections. Steroids can affect the TM by increasing ECM deposition and decreasing ECM breakdown by inhibiting endothelial cell phagocytosis[49,50]. This increases resistance to drainage of the aqueous humor, reducing aqueous filtration, which in turn, increases IOP[51].

In a study among diabetic macular edema (DME) patients who received an intravitreal dexamethasone (IVD) implant (Ozurdex, Allergan Inc, United States), about 3.6% presented with an IOP ≥ 25 mmHg at 1 month follow-up, 7.2% at 2 months and 2.4% at 3 months. Patients whose IOP was raised by > 30% or ≥ 20 mmHg at one month post-implantation subsequently developed OHT with statistical significance[52]. Shorter axial length[53] and younger age[54] were associated with OHT occurrence after implantation. There was no significant difference between vitrectomized and non-vitrectomized eyes[52]. Postinjection IOP rise after IVD implant can be classified as > 35 mmHg, > 30 mmHg, > 25 mmHg and > 10 mmHg elevation from baseline. In DME patients, this rise has been observed in 2.4%, 3%, 7.3% and 6.7% patients respectively, most of whom required IOP-lowering medication for maintenance, although none needed glaucoma filtering surgery[55]. Overall, about 17% of IVD administered eyes develop OHT[56].

Intravitreal Triamcinolone Acetonide (IVTA) is also used in the same manner, and 28% of such patients may develop OHT[56]. It has been found that the propensity of patients to develop IOP elevation to 24 mmHg is much higher if the baseline IOP is 15 mmHg[57]. However, IVTA use is indicated mostly in patients with additional risk factors, viz. pseudophakic and vitrectomized eyes, conditions which are predisposed to the occurrence of OHT[58,59]. It is also reported that repeat injections may or may not increase the IOP beyond 30 mmHg[48,60].

Risk factors for steroid-induced IOP rise due to topical steroid eye-drops after intraocular surgery for cataract and vitreoretinal disease include pre-existing primary open-angle glaucoma or glaucoma suspect, young or old age, type I DM and high myopia[48].

In the setting of vitreoretinal surgery, post-surgical IOP elevation has been found to be more with the use of 20 gauge pars-plana vitrectomy and expansile gases for internal tamponade; the number of retinal endolaser spots are associated with early IOP rise after surgery[61]. In the long term, neovascularization may ensue and OHT may develop even without retinal endolaser, subsequently causing reduction of visual function and glaucoma.

Intraocular silicone oil injection has also been found to promote IOP elevation, especially in cases of oil overfill, absence of inferior iridectomy or emulsified silicone oil migrating to the anterior chamber and forming a hyperoleon causing TM damage[62]. Removal of silicon oil has been found to contribute to significant reduction of IOP level in PDR patients taken up for vitreoretinal surgery without preoperative retinal laser due to conditions precluding it. This change is insignificant in patients who have undergone preoperative laser. This might be related to associated pre-existing vascular changes in the conditions which require laser photocoagulation, but an understanding of the pathophysiology in this condition is unclear. It may point to a contribution of neovascularization of the iris, angle and retina in the pathogenesis of OHT in eyes which undergo vitreoretinal intervention in the setting of PDR[63].

EFFECT OF COMORBIDITIES ON OHT IN DIABETIC PATIENTS

While IOP has been directly implicated as an independent risk factor for DR, the retinopathy in DM is also related to comorbidities, like hypertension and heart disease that are also correlated with OHT (Figure 3). The metabolic syndrome as a whole has been implicated to increase the propensity of eyes to develop OHT, primarily associated with complex vascular changes causing alterations in blood and ocular perfusion pressures which may or may not be clinically detectable[64]. In a study, approximately 2% of cases with DM and hypertension without retinopathy were found to have OHT[65].

Figure 3 Systemic comorbidities influencing ocular hypertension in diabetes mellitus. IOP: Intraocular pressure; TM: Trabecular meshwork.

Dyslipidemia and dyscholesterolemia are also associated with increased IOP which may or may not culminate in glaucoma[66]. Altered ratio of various lipids could cause rise in episcleral venous pressure and blood viscosity, thereby reducing the aqueous outflow[67]. Altered meibomian gland secretions in dyslipidemia affect the stability of the tear film on the ocular surface by causing evaporative dry eye disease, which has been found to be associated with increased IOP[68].

The effect of liver disease on IOP levels is poorly understood. In a study, patients with elevated IOP were found to have significantly increased gamma-glutamyl transferase and total bilirubin and lower alkaline phosphatase values[4]. In similar studies, a linear relationship has been found between IOP levels and alcoholic as well as non-alcoholic fatty liver disease[69,70]. Altered gut permeability may be responsible for ectopic immune stimulation in the liver, which, through poorly understood autoimmune mechanisms, may affect IOP levels[28].

Bone disorders like osteoporosis associated with altered calcium and phosphorus levels may also affect IOP. However, the pathophysiology is poorly understood and may be related to the function of the aqueous producing epithelium of the ciliary body, or the aqueous drainage mechanism[71]. A transient receptor potential Vanilloid 4 is a central channel for calcium ion. It is a mechanoceptive receptor in TM cells which activates by stretch to cause cytoskeletal remodelling increasing TM resistance thereby causing increase in IOP[72,73]. It has been found in patients of chronic kidney disease with increased phosphorus levels, that phosphorus itself may also be deposited in the TM thereby increasing outflow resistance[74].

The effect of ocular surgery on the increased propensity to develop OHT generally dictates that the severity of inflammation following surgery appears to be a major factor influencing the post-surgical IOP rise[75]. For example, DM patients often suffer from corneal ulcers and corneal scars, which may be treated by therapeutic or optical penetrating keratoplasty, respectively[76]. High preoperative IOP and combined keratoplasty with removal or exchange of an intraocular lens (IOL) are definitely associated with post-surgical IOP rise. Aphakia and pseudophakia with anterior or posterior chamber IOL implantation are also definitely associated with increased IOP when compared to surgeries which preserve the natural crystalline lens. Glaucoma in contralateral eyes, indication of bullous keratopathy, African American descent, preoperative treatment with cyclosporine or olopatadine 0.1%, postoperative treatment with prednisolone acetate 1%, and combined surgery in general have also been found to be probably associated[77].

MEASUREMENT OF IOP IN DIABETIC PATIENTS

In a discussion of the occurrence of OHT in diabetic subjects, it is also imperative to discuss the various considerations for accurate measurement of IOP in this condition.

In the present era, IOP measurement (tonometry) is possible through contact and non-contact methods. Non-contact tonometry (NCT) is an acceptable method for screening of OHT but the accuracy does not approach the gold standard, the latter being Goldmann Applanation Tonometry (GAT). NCT can be used for routine screening of OHT in diabetic patients[78].

GAT, being a contact procedure, carries a risk of microbial keratitis due to improper disinfection of the GAT prism. The setting of increased propensity for corneal epithelial dysfunction and increased incidence of corneal ulcer in diabetic patients, especially those with poorly controlled diabetes, is an important consideration[79]. GAT also entails the use of topical anaesthetic agents like proparacaine 0.5% which are epitheliotoxic, and the decreased corneal sensation may also increase the risk of residence of microbes associated with the GAT prism, or foreign body or fingernail trauma occurring for a short duration after the procedure[80].

The GAT prism must be disinfected prior to its use in diabetic patients. It is preferable to use freshly opened eye drops and fluorescein strips, respectively, for anesthetizing and staining the ocular surface. It is also crucial to note that due to these special circumstances, the patient must clearly be instructed to avoid any trauma, not to rub the eyes or go outdoors up to 30-45 minutes after the procedure. The procedure of contact tonometry must be followed by instillation of a topical antibiotic agent for prophylaxis against any microbes which may have been inoculated on the ocular surface[80].

The IOP measurement may be aided by the measurement of CCT (or pachymetry), allowing correction of the IOP for corneal thickness, but there are numerous caveats to IOP measurement which cannot be compensated for by CCT alone[81]. The CCT of diabetic patients is reported to be higher due to corneal stiffening by accumulated advanced glycated end-products causing collagen cross-linking by covalent bond formation resulting in high IOP. Hence this may increase the readings taken by GAT[79]. A careful consideration of the correct IOP recording must be documented prior to instituting therapy in these cases.

Treatment of OHT in diabetes

The OHT study showed that, in general, subjects aged 40-80 years with OHT showed cumulative probability of developing primary open-angle glaucoma to be 4.4% in medication group and 9.5% in observation group over 5 years. In other words, only one case of glaucoma can be prevented for 100 patients treated for OHT. There were no systemic or ocular risks associated with ocular hypotensive medication. However, nonselective beta-blockers like topical timolol maleate 0.5% should be used with caution in diabetic patients, as they may cause additional fall in plasma glucose resulting in neuroglycopenic symptoms[82].

CONCLUSION

OHT, defined as increased IOP (> 21 mmHg) in eyes without optic disc changes or visual field changes, is a condition which puts an eye at higher risk of developing glaucomatous optic neuropathy. OHT is one of the important concerns in DM even in the eyes which do not have DR changes. The understanding of the complex interplay of pathophysiologic risk factors is important for early identification and management of patients predisposed to this condition. DM, arterial hypertension, and elevated serum lipid concentrations should be checked for in ocular hypertensive subjects. Optimum control of systemic parameters with careful follow up of ocular health of patients with diabetes is important so that medication can be instituted timely to prevent glaucomatous damage in patients with co-existing OHT.