June 13, 2025
12 min learn
Key takeaways:
- Variations between the eyes of women and men might affect illness susceptibility and signs.
- Earlier exclusion of ladies in medical trials has resulted in an information hole.
There are delicate however vital variations within the morphology and biochemistry of the attention between women and men.
These variations might have an effect on illness susceptibility, signs and development, response to remedy, outcomes of surgical interventions and even the method of visible notion. In all areas of drugs, extra consciousness of intercourse and gender variations and extra research are wanted to develop more and more personalised care and focused remedies, transferring away from the previous androcentric perspective.
Earlier exclusion of ladies in medical trials has resulted in an information hole throughout drugs, in keeping with Sotiria Palioura, MD, MSc, PhD. Picture: Courtesy of Sotiria Palioura, MD, MSc, PhD
“Till 1993, the insurance policies by the NIH and FDA in the US both excluded or strongly discouraged the participation of ladies in medical trials, particularly girls of childbearing age,” Sotiria Palioura, MD, MSc, PhD, mentioned. “That implies that loads of the information we’ve now in drugs is predicated on solely half of the inhabitants.”
Even within the laboratory, all research have been carried out on male mice for worry that hormonal adjustments in feminine mice would have an effect on research outcomes.
The implications of an information hole
The rationale behind the exclusion of ladies from medical trials was to guard them from unknown drug results, particularly throughout fertile age and being pregnant, however the results of this coverage was a large knowledge hole.
“The rules we use in drugs to diagnose sure situations, the thresholds in our testing and the drug dosages have been all developed based mostly on male physiology, the idea being that the outcomes could be universally relevant,” Palioura mentioned.
This false assumption resulted in essential long-lasting penalties.
“In pharmacology, we’ve discovered the arduous means that ladies metabolize some medication in another way as a consequence of variations in physique composition and liver enzyme exercise, and that partly explains why girls typically expertise extra unintended effects from medicines that have been primarily initially examined for males,” she mentioned.
One other consequence was that the cutoff worth for troponin ranges indicative of a possible coronary heart assault, initially calibrated utilizing male topics, led to loads of missed coronary heart assaults in girls.
Variations between men and women at the moment are rising by research in numerous fields of drugs. In cardiology, it has been proven that ladies typically current with signs of coronary heart assault that aren’t so frequent in males, corresponding to again and jaw ache, fatigue, nausea and shortness of breath. In neurology, Alzheimer’s illness and a number of sclerosis have been discovered to be extra prevalent in girls, probably as a consequence of hormonal and immune system variations.
In ophthalmology, there’s additionally a rising physique of analysis addressing the variations between female and male eyes.
“A number of research have proven that ladies are likely to have shorter axial lengths, steeper corneas and shallower anterior chambers, and that, in fact, has loads of implications after we do biometry for IOL calculations,” Palioura mentioned. “The danger of angle-closure glaucoma is completely different in girls than in males. However apart from that, we all know that dry eye illness is far more frequent in girls, particularly round menopause, and analysis by real-world registries has explored sex-based variations in outcomes for cataract surgical procedure and anti-VEGF remedy.”
Variations in biometric measurements
Swedish Nationwide Cataract Register knowledge from the early 2000s, Anders Behndig, MD, PhD, and colleagues discovered that the biometry prediction error was bigger in girls than in males.
Anders Behndig
“This was between 2004 and 2006, and from 2007, this distinction had mysteriously disappeared,” he mentioned. “Wanting deeper into these knowledge, in a research that we revealed in 2014, we realized that the change occurred after we switched from the SRK-T formulation to the Haigis formulation for IOL calculation.”
The SRK-T formulation, which was utilized in practically all cataract surgical procedures in these early years, was calibrated for an eye fixed with a slightly flat cornea and lengthy axial size. By analyzing the biometry knowledge within the registry, it grew to become clear that, for a similar refraction, girls have a barely steeper cornea and a shorter eye whereas males have a flatter cornea and an extended eye.
“As it’s typically the case in drugs, the SRK-T formulation had been higher calibrated for males than for ladies,” Behndig mentioned. “With the newer Haigis formulation, one of many principal variations was that we began to measure the anterior chamber depth as a substitute of simply estimating it. This led to raised outcomes for each men and women, and the distinction disappeared.”
After the research was revealed, there was a fast swap to the newer formulation amongst cataract surgeons in Sweden.
“It must be added that the variations between men and women are very small, and it wouldn’t have been attainable to seek out them if we hadn’t had the big quantity of information accessible by the registry,” Behndig mentioned. “Even in a small nation like Sweden, we do monumental quantities of cataract procedures, and even when from a person’s perspective the variations are fairly small and go unnoticed, they develop into obvious whenever you multiply them by very huge numbers.”
Even higher formulation are in use these days, and people variations in outcomes have disappeared. Nonetheless, these previous knowledge replicate the final precept that registries are critically essential to take a look at massive numbers, discover small errors and regulate them.
“Small errors are hidden for the person surgeon in the event you don’t collect knowledge from loads of different surgeons,” Behndig mentioned. “For those who uncover {that a} male affected person has a little bit bit higher probability than a girl to be spectacle-free after surgical procedure, then it’s a must to do one thing about it.”
The correlation between size and quantity
Some variations in ocular biometry parameters between female and male sufferers exist at delivery, Marie-José Tassignon, MD, PhD, mentioned.
“Child boys have longer axial size than child women,” she mentioned. “And later in life, the male eye is longer than the feminine eye for a similar refractive error.”
Marie-José Tassignon
On the College of Antwerp, Belgium, collectively together with her former PhD scholar Jos Rozema, now head of the Visible Optics Lab Antwerp, Tassignon has been conducting analysis on ocular biometry inside the native inhabitants.
Controlling confounding results was not straightforward within the various inhabitants of Belgium, with a big presence of individuals of Asian and African origins and loads of interracial mixing.
“Nonetheless, we may conclude that there was a distinction between feminine and male eyes,” Tassignon mentioned. “For a similar refractive error, they’ve completely different parameters, together with the axial size, the connection between axial size and corneal radius curvature, and the lens thickness.”
These parameters must be taken into consideration when choosing an IOL slightly than counting on simply formulation and refractive targets.
A distinction in axial size additionally correlates with a distinction within the quantity of the attention and due to this fact the quantity of the vitreous, she mentioned.
“Quantity is a parameter that’s far more vital than size. After we measure the attention, would it not not be higher to assume volumetrically as a substitute of considering solely in millimeters?” Tassignon mentioned.
Loads but to be found
Precisely figuring out the efficient lens place is essential to the success of cataract surgical procedure. If sizes and volumes of eyes are completely different in males in contrast with girls, that implies that the efficient lens place can even be completely different.
“In all my profession, I’ve by no means relied on only a formulation,” Tassignon mentioned. “I at all times have a look at all of the parameters: the axial size, the anterior chamber, the curvature and the stiffness of the cornea, and the place of the crystalline lens based mostly on OCT. We’re fortunate to have IOL formulation to assist us, however we aren’t there but. We’d like extra info.”
The zonules, for example, are “a giant query mark.” They’re fabricated from collagen, and collagen deteriorates with age. The ligament of Wieger will detach with time, resulting in detachment of the anterior hyaloid. Due to this fact, the water surrounding the capsular bag-lens advanced can be diluted and supply much less help.
“So, age-related adjustments of the attention, male vs. feminine variations and adjustments within the biometrical parameters — all this makes it a little bit advanced for us to fulfill all varieties of eyes and all our sufferers. We have now to review additional,” Tassignon mentioned.
Vitreous liquefaction can be a pure course of that happens with age. There’s at the moment no means to measure the diploma of viscosity of the vitreous, which can additionally differ between women and men.
“We will guess the place we’re with the liquefaction course of by assessing the mobility of the vitreous on the slit lamp or trying on the OCT and even ultrasound. However what we need to obtain is a quantification of viscosity, and we’ve no devices to measure that at current,” Tassignon mentioned.
Simply the one easy query — Is there a distinction between women and men? — can open up the chance for a lot of new research which may play a pivotal function in advancing eye care, she mentioned. “Fortunately, it’s not but completed. There’s at all times one thing new we will uncover.”
Similar signs, completely different etiologies
The identical signs could also be indicative of various situations in girls vs. males, in keeping with Anat Galor, MD, MSPH. As a cornea and ocular floor illness specialist, she sees many sufferers with ocular ache, however the etiology is usually completely different.
“Autoimmune situations corresponding to Sjögren’s syndrome are far more frequent in girls, whereas traumatic mind harm is extra frequent in males,” Galor mentioned. “If you take a giant class like ocular ache, causes are completely different, and people causes have completely different gender predilection.”
Anat Galor
There are additionally variations within the frequency and severity of ocular ache between women and men, which can be as a consequence of greater sensitivity to ache in girls. In a evaluate article, Galor and co-authors talked about a research by Li and colleagues wherein girls confirmed better ache sensitivity than males amongst 287 respondents to a questionnaire.
With respect to the frequent perception that dry eye illness extra incessantly impacts girls than males, Galor took a step again and mentioned that it’s true that immune-mediated dry eye is extra frequent amongst girls, however meibomian gland dysfunction-related dry eye is equally distributed throughout men and women.
By trying on the underlying causes of particular signs, ophthalmologists will help within the analysis of systemic illnesses.
“In a girl with an inflammatory eye situation, it is very important ask your self, ‘Might this be a part of a systemic situation?’ In girls, it’s typically an autoimmune course of that shouldn’t be missed,” Galor mentioned.
Her recommendation to ophthalmologists is to grasp the epidemiology of systemic illnesses that current with signs or indicators within the eye and pay attention to which of them are extra frequent in girls or males.
“However don’t ignore the truth that the opposite gender will also be affected,” she mentioned. “It’s essential to contemplate gender however not to try this completely as a result of there are additionally different elements that come into play.”
Existence, hormones and response to therapies
There are three areas that need to be thought of when diagnosing eye situations, in keeping with Galor: environmental elements and way of life selections, ocular elements, and ocular manifestations of systemic illness.
“Any of these can have male-female disparities,” Galor mentioned.
Ladies put on make-up, whereas most males don’t, and make-up merchandise typically include chemical compounds that in the long run might be unhealthy for the attention. Lash extensions additionally have an effect on the ocular floor, and medical therapy to enhance lash size may cause the lashes to show in and trigger vital discomfort, she mentioned.
In each women and men, hormone receptors are current all through the ocular floor. Hormonal adjustments within the perimenopausal age may predispose girls to creating dry eye, whereas androgen deficiency can contribute to dry eye in males.
“There are various examples the place males who’ve prostate most cancers and go on androgen blockers have meibomian gland dysfunction,” Galor mentioned.
As well as, there may be gender variations within the response to therapies, however research on dry eye illness medication give solely the information on lively therapy vs. placebo and don’t section sufferers into responders and nonresponders.
“It will be fascinating to grasp, inside the research populations, if males or girls have been extra probably to answer a selected agent. The information are there however should not offered,” Galor mentioned.
There are nonetheless questions that must be answered and research that must be carried out, however women and men can’t be put in the identical actual class as a result of they’ve completely different ache notion, completely different danger charges for various illnesses, and completely different environmental publicity.
“We have now to contemplate these variations after we put collectively an general plan for the affected person,” she mentioned.
Immune responses
Palioura, who’s a cornea, ocular floor and cataract specialist, noticed in her observe that ladies have extra extreme and extra symptomatic dry eye, typically with minimal medical indicators.
She additionally observed that ladies have a extra sturdy inflammatory response after surgical procedures corresponding to cataract surgical procedure, corneal transplantation and pterygium elimination.
“They are going to have extra redness, discomfort, typically even delayed therapeutic, and that is in all probability due to variations within the immune system exercise,” Palioura mentioned. “Ladies are likely to mount stronger immune responses, which protects them from infections, however on the identical time, they are often counterproductive for tissue therapeutic.”
In consideration of this, Palioura’s preoperative planning and preoperative method for cataract surgical procedure are extra aggressive in girls.
“I optimize the ocular floor extra aggressively with a purpose to keep away from any errors in IOL calculations, and postoperatively, I’m extra vigilant about irritation in feminine sufferers,” she mentioned. “I might even see them extra incessantly and regulate my topical steroid routine to be extra aggressive if I see that they’ve a extra sturdy inflammatory response.”
Earlier in her profession, Palioura encountered instances wherein girls had refractive surprises after cataract surgical procedure as a result of their biometric parameters fell outdoors what conventional formulation accounted for. She additionally encountered conditions wherein girls’s dry eye signs have been dismissed, resulting in loads of frustration and dissatisfaction.
“These gaps in our understanding have been irritating not just for our girls sufferers but in addition for us physicians. These variations additionally emphasize the necessity to embody intercourse as a variable in our future research,” she mentioned.
AI reveals intercourse variations in retina
AI will help determine options within the retina which are predictive of organic intercourse.
“I’ve greater than 30 years of expertise in inspecting retinas, however in the event you present me an image of the retina, I can not say that is male or feminine,” Christina N. Grupcheva, MD, PhD, mentioned. “Instantly, synthetic intelligence began to tell apart the gender of the retina, and we requested ourselves: The place precisely is the distinction?”
Christina N. Grupcheva
Impressed by AI’s efficiency, a number of teams of researchers have tried to spotlight and map out the areas that AI fashions use for intercourse classification, suggesting that the retinal vasculature, the peripapillary space and the macula are attainable sources of this info.
“Very first thing is vasculature. Males have extra vessels with a wider vascular branching,” Grupcheva mentioned. “Then we’ve the peripapillary space, which is often darker in males. We do not know what the measures are that AI fashions use, however we guess that this peripapillary space stands out as the second essential supply of intercourse biomarkers. And in the case of the macula, apparently, males have a thicker macula than girls of the identical age group. Different research have seemed on the construction of the retina and located that males have a thicker retinal nerve fiber layer.”
This info, when utilized by human observers inside research, improved the flexibility to detect intercourse variations above the 50% threshold.
“We’re nonetheless removed from the sensitivity of AI, which is continually rising and is now near 100%,” Grupcheva mentioned.
Shade imaginative and prescient
These findings may have essential implications on epidemiology, the invention of biomarkers and the event of prediction fashions of retinal illnesses. They could additionally reveal the the reason why some retinal illnesses, like macular degeneration, are extra frequent in girls, and others, like diabetic macular edema, are extra frequent in males. This might result in a deeper understanding of evolutionary traits that distinguish women and men.
“If we return to the hunter-gatherer period, the person, who was the hunter, wanted to have superb distinction sensitivity for catching prey throughout the night time and superb coordination between eye and hand. The lady, who was the gatherer, wanted higher shade sensitivity to choose up small fruits,” Grupcheva mentioned.
Shade blindness is way much less frequent in girls, and several other research have proven that ladies have higher shade discrimination; some feminine topics have tetrachromacy, sensitivity for ultraviolet colours, which explains this phenomenon, she mentioned.
Grupcheva shared the anecdote of a uncommon case of shade blindness she present in a feminine affected person. She labored in a strawberry farm in the UK, and her employer threatened to fireside her as a result of she stored selecting inexperienced strawberries.
“She got here to me, I evaluated her shade deficiency, and I prescribed for her a contact lens that enhanced shade notion that she would put on in the best eye,” she mentioned. “Her efficiency was instantly higher, and to thank me, she introduced from the UK a giant basket of strawberries.”
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For extra info:
Anders Behndig, MD, PhD, of Umeå College Hospital, Sweden, might be reached at anders.behndig@umu.se.
Anat Galor, MD, MSPH, of Bascom Palmer Eye Institute, Miami, might be reached at agalor@med.miami.edu.
Christina N. Grupcheva, MD, PhD, of Medical College of Varna, Bulgaria, might be reached at cgrupcheva@gmail.com.
Sotiria Palioura, MD, MSc, PhD, of Bascom Palmer Eye Institute, Miami, might be reached at sotiria.palioura@gmail.com.
Marie-José Tassignon, MD, PhD, of Antwerp College Hospital, Belgium, might be reached at mj.tassignon@gmail.com.
Sources/Disclosures
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Disclosures:
Behndig, Galor, Grupcheva, Palioura and Tassignon report no related monetary disclosures.
