Disease-a-Month 67 (2021) 101134

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Disease-a-Month

journal homepage: www.elsevier.com/locate/disamonth

Diabetic cataracts
Mitchell J. Greenberg, MD, Sonya Bamba, MD∗
Cook County Health and Hospital Systems, United States

Introduction

As the prevalence of obesity continues to increase in the United States and worldwide, so
do the number of individuals with diabetes mellitus (DM). With an estimated current impact of
425 million people and a projected 629 million affected by 2045, diabetes stands as one of the
world’s major health challenges for years to come.1,2 Cataracts, the leading cause of blindness
globally, are of particular interest within this disease cohort, as diabetics remain susceptible to
2–5 times higher incidence and earlier development.
Up to 20% of all cataract surgery is performed on diabetic patients. Surgery on its own has
been known to, at the minimum, increase inflammation within the eye, and possibly increase
the progressive risk of diabetic-related retinopathy. With variable access to proper health re-
sources around the globe, prevention of diabetic cataracts has been thrust into the spotlight as
a high health burden in the primary care and ophthalmology realms of practice.

Epidemiology

Diabetics have long been known to have an increased risk for and earlier development of
cataracts. The Wisconsin Epidemiological Study of Diabetic Retinopathy found that the 10-year
risk of cataract formation was 8.3% and 24.8% in type 1 and 2 diabetics, respectively.3 In ad-
dition, the Framingham Eye Study reported that the relative risk of cataract before age 65 has
been shown to be as high as four-fold, with poor blood glucose control and extended length
of disease as the main contributing factors.3,4 These same studies have also pointed to poten-
tial reversal of cataract formation for type 1 diabetics in particular, assuming tight glucose and
metabolic control.

∗
Corresponding author.
E-mail address: sonya.bamba@gmail.com (S. Bamba).

https://doi.org/10.1016/j.disamonth.2021.101134
0011-5029/© 2021 Elsevier Inc. All rights reserved.
2 M.J. Greenberg and S. Bamba / Disease-a-Month 67 (2021) 101134

Fig. 1. Increased glucose leads to rapid production of sorbitol and an osmotic swelling effect within the lens. Increased
free radicals are produced as a result, degrading lens fibers in the process.

Multiple studies have shown a clear relationship between highly glycated hemoglobin and
posterior subcapsular cataracts (PSC) as well as cortical cataracts (CC), with a relatively weak
association to senile nuclear cataracts (SNC). Snowflake cataracts, rapidly progressive subcapsular
opacities, have been strongly linked to young type 1 diabetics with uncontrolled blood sugars.2,5

Pathogenesis

The aforementioned link relies on multiple pathways that result in both swelling of the lens
and cataract formation itself. Through the aldose reductase (AR) pathway, glucose is reduced to
sorbitol within the lens.1,4 As sorbitol accumulates in diabetics faster than it can be reduced to
fructose, water follows the now hyperosmotic gradient to create a swollen lens. This is known
as the “Hyperosmotic Effect”. Apart from altering the refractive index of the eye, thus changing
its ability to focus, sorbitol is known to degrade cortical lens fibers directly.
Multiple studies have shown that this osmotic stress on the lens increases apoptotic rates
within the epithelial layer of the capsule. After swelling from water influx, the epithelial cells
burst. Mice with overexpression of aldose reductase and phospholipase D (PLD) were prone to
cataract formation over control subjects with elevated PLD alone.
The polyol pathway (Fig. 1) is also responsible for increased free radicals within the lens
as a result of rapidly fluxed glucose levels in diabetics.3,6 As reactive oxidative species (ROS)
increase, so does the rate of damage to lens fibers. Elevated glucose levels in aqueous humor
directly glycate lens proteins, triggering more ROS formation. Made worse is the direct inhibitory
impact of glucose on antioxidant enzymes such as Superoxide Dismutase 1 (SOD1), triggering
the degenerative cycle of diabetic cataract formation.

Timing of surgery

Prior to the advent of contemporary retinal imaging techniques such as Optical Coherence
Tomography (OCT) and preventative treatment strategies for diabetic retinopathy, the prevail-
 M.J. Greenberg and S. Bamba / Disease-a-Month 67 (2021) 101134 3

ing theory was to delay surgical intervention for diabetic cataracts until visual acuity worsened
beyond 20/100 to reduce the risk of inflammation and macular edema complications.4
A more aggressive approach has become popularized, recommending surgical intervention
at an earlier point, and thus providing a clearer window to the posterior segment of the eye
for retinal specialists. Diagnostic modalities like OCT are optimized with clear views. Likewise,
panretinal photocoagulation (PRP) laser and anti-VEGF injections for aberrant neovascularization
are significantly more effective when the provider is treating a pseudophakic patient. Long-term
visual outcomes have shown to be improved when ophthalmic diabetes is treated in this order.

Preoperative management

Preoperative care in diabetic patients is critical for optimizing visual acuity outcomes. As
mentioned previously, lens convexity increases when blood glucose levels are elevated, creat-
ing an artificially myopic eye. Corneal topographic changes may occur as glucose levels fluctu-
ate and may alter keratorefractive measurements that take place during pre-operative testing.4,5
Measurements of the refractive error and the shape of the eye are crucial to choosing an appro-
priate lens implant, so these parameters must be stable in order to provide the best outcome.
Thus, strict diabetic control should be emphasized prior to surgical evaluation.
Consultation with vitreoretinal specialists is also encouraged, as pre-existing diabetic macular
edema (DME) may worsen quickly after cataract surgery via increased vascular permeability. If a
posterior view is available, OCT may be encouraged to determine the extent of fluid accumula-
tion in the back of the eye. At this point, PRP laser and/or anti-VEGF intravitreal injection timing
must be discussed jointly. Some studies have shown high efficacy of peri-operative anti-VEGF
injection.
Similarly, if neovascularization of the iris (NVI) is present, the possibility of rapid closure of
the angle from fibrosis and scarring may result in neovascular glaucoma (NVG). NVG may be
treated with topical medications, oral carbonic anhydrase inhibitors, anti-VEGF injection, surgi-
cal procedures, or a combination of these. Surgical management of the cataract must take into
account the need for treatment of coexisting NVG. Cataract extraction itself may be beneficial, as
a way to manage the intraocular pressure, but surgical planning is imperative, as the technique
utilized in surgery may be different when accounting for NVG. Perioperative diode cyclophoto-
coagulation laser has also shown promise for these patients.

Cataract surgery

Phacoemulsification, a surgical technique designed to break up the cataractous lens by way

of ultrasound and then extract the lens in pieces, has been the method of choice since the mid
1990 s. Although superior to extracapsular methods in terms of post-operative complications,
special considerations must be taken for diabetic patients. Limbal incisions, which provide access
to the anterior chamber, should be minimized in terms of size due to the impaired healing
capability of uncontrolled diabetics.5,6 Anterior capsular phimosis is seen more frequently in this
patient population; thus the anterior capsulorrhexis (circular opening created intraoperatively to
access the lens) should be larger than in non-diabetic cases.
Microvascular ischemia may lead to pupillary nerve dysfunction, making pre-operative dila-
tion difficult. The surgeon should be prepared with pupil expansion devices or intraoperative
pharmacologics such as lidocaine with epinephrine to widen access to the lens.1,3
In terms of intraocular lens (IOL) choice, large diameter implants facilitate a better periph-
eral retina view for evaluating for potential diabetic retinopathy. Additionally, the material of
lens utilized should be considered with respect to future vitreoretinal surgical procedures. Hy-
drophobic IOL’s do not adhese silicone, a commonly used entity during pars plana vitrectomies.
These lenses are also significantly less prone to posterior capsular opacification (PCO, Fig. 2),
4 M.J. Greenberg and S. Bamba / Disease-a-Month 67 (2021) 101134

Fig. 2. Posterior capsular opacification.

Fig. 3. Optical Coherence Tomography (OCT) image showing cystoid macular edema and serous retinal detachment after
cataract surgery.

a common post-operative complication, relative to their hydrophilic counterparts, which may

negate the need for future procedures that could also potentially stimulate harmful inflamma-
tion.3,6

Postoperative management: visual outcomes and complications

Visual outcomes are favorable in diabetics with good glycemic control and generally com-
parable to non-diabetics if little or no retinopathy is found pre-operatively. Phacoemulsification
has significantly decreased the incidence of postoperative complications in terms of inflamma-
tion and pain, compared to older extracapsular or intracapsular techniques.
However, if clinically significant macular edema (CSME, Fig. 3) or other signs of severe DR are
found before surgery, the patient may be at risk for poor functional improvement and rapidly
progressive retinopathy.3 Macular edema is known to accelerate after cataract surgery and neo-
vascularization can seed into the vitreous causing hemorrhage and/or tractional retinal detach-
ments. Thus, preoperative testing to determine proliferative vs. non-proliferative DR is critical to
mitigate these risks.3,4 Perioperative intra-vitreal injections have been the focus of several stud-
ies to decrease PDR progression and optimize visual outcomes. Peri- and postoperative NSAIDS
 M.J. Greenberg and S. Bamba / Disease-a-Month 67 (2021) 101134 5

have also been shown in multiple studies to decrease the incidence of macular edema progres-
sion postoperatively.
Within three months of surgery, a comprehensive retinal evaluation should take place includ-
ing OCT imaging and a dilated fundoscopic exam (DFE). Centerpoint thickness in the macula is
a commonly used value to evaluate the degree of macular edema present in a patient with pre-
operative DME. If necessary, the retina specialist may employ additional anti-VEGF injection or
PRP laser at this time.

Alternative treatments

Aldose reductase inhibitors (ARI), which block the reduction of glucose to sorbitol, have been
hypothesized as potential agents to delay and even prevent the onset of diabetic cataracts in
animal models.4 In diabetic rats, flavonoids have been shown to reduce sorbitol accumulation
within the lens. Reniristat, a potent ARI, has been studied extensively in India and has shown
promise for preventing diabetic cataracts in mice without signs of lens swelling or fibrosis.
Antioxidants have also been studied as potential agents to reduce the rate of cataract forma-
tion secondary to toxic ROS in the diabetic eye. Vitamin E, at a dose of 500 IU daily, in con-
junction with insulin treatment, has shown some promise in this regard. Continued research is
needed to validate these findings in humans.4

Conclusion

As the number of diabetics worldwide continues to increase at an alarming rate, so will the
incidence of cataract formation. These individuals need to be evaluated in a multidisciplinary
fashion between primary care physicians, cataract surgeons and vitreoretinal specialists. Pre-,
peri- and postoperative consultation as well as fluid communication between these practition-
ers is required to ensure optimal visual outcomes long-term. The advent of phacoemulsification
has proved a setting for safer and more effective surgery, paving the way for excellent visual
outcomes.

References
1. https://pdfs.semanticscholar.org/dd1d/7dd7992ae67546b22744f1feaf5d63aa2b95.pdf
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173035/
3. https://www.wjgnet.com/1948-9358/full/v10/i3/140.htm
4. https://www.hindawi.com/journals/joph/2010/608751/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589218/
6. https://www.ncbi.nlm.nih.gov/pubmed/7585233