 All right. Sorry I'm late. It's a boring lecture anyway, so you only have to listen to half of this whole thing. You're going to sell us on this lecture tomorrow. I haven't looked at these slides for two years. So we're talking about sort of the basics of the BCSE, right, the anatomy, physiology, all the good stuff. Let's see. Anatomy of the lens. There's no blood supply or innervation. So it depends on aqueous for nutrient delivery and waste removal. We know what it does, it reflects light. Some interesting concepts, I guess you look at it with aging. In terms of changes, sometimes there's a myopic shift, sometimes there's a hyperopic shift. We know it's always increasing in curvature, but the very changes in index of refraction can alter the actual refractive effect of that. Size at birth versus size at adults. So those are sort of important anatomic considerations. If you're a cataract surgeon, just remembering that in adult size, it's usually about five millimeters thick at most. So you've got about five millimeters of depth before you're puncturing or posturing a capsule with whatever instrument you're using. All right. The capsule, elastic membrane type 4 collagen, just remember it's thin as posteriorly. Two to four microns, pretty impressive how strong it is despite its thin nature there. You can see it's thickest equatorial and centrally about 14 microns. Zonules, microfiberals, composed of elastic tissue. They originate from the non-pigmented epithelium of the ciliary body. They insert it in a continuous fashion in the equatorial region. You can see they insert just a little bit more central anteriorly versus posteriorly. And with age, of course, the fibers regress. The equatorial fibers will regress, leading mostly just anterior and posterior fibers. The lens epithelium is a single layer. Of course, there's active replication in the anterior equatorial region, as we all know. The newly formed cells, as we know, they migrate equatorially and posteriorly, forming new lens fibers, losing their organelles through that process. And of course, because they have no organelles, they depend on glycolysis. Which, you know, if you remember that from your chemistry, biochemistry class. Let's see. So, let's highlight here. Of course, no cells are lost from the lens. The oldest form the nucleus. So you'll see that fetal or embryonic suture pattern. The newest form the outermost aspect of the cortex. We've seen the lens sutures on those who've looked on Slitlamp exam, the interdigitations there, the apical and basal cells. We see optical zones when you look at a lens. So you might notice that there's sort of this delineation of an endonucleus, the central lens component, versus the epinucleus or cortical material. When you look at cataracts, sort of a similar finding, except it's not a clear lens, obviously. It's clouded to some degree. There's no morphologic distinction between the cortex and nucleus. Though, you know, we have these surgical delineations that we talk about or discuss when you actually look at it from a pathology assessment. Histologically, there's really no differentiation. The lens up to the other cells, those lens cells look the same. Let's see. Crystalline proteins that make up a lot of what is left over once the lens has eliminated its organelles. You can see some fascinating concepts about it, and maybe you should read about this sometime. It's not super exciting. As that, I know as you age, you start to lose some of the... Let's see. It says here, maybe it's the next slide here. Never mind. Memorandum structural proteins inside of skeletal proteins. Anything a highlight that I could take off of here while you're reading it? Here it is. Yeah, the increase of water and soluble proteins with age. This is actually important to understand as we get older. Protein aggregates into large particles that become water and soluble. That's going to result in opacity, reduced clarity, or cataract. They scatter light. Of course, a certain amount of this process appears to be normal with maturation of lens cells. The scene in clear lenses with the excess of it results in the cataract formation that we see with age. There's a reasonably good correlation between the amount of insoluble protein and brunescence of a cataract. Loss of the reduced form of glutathione as you get oxidative stress with these disulfide bonds. Pigment formation, cross-linging, et cetera. It results in cataracts. Let's see. Carbohydrate metabolism. We talked about it requiring glycolysis because it is essentially anaerobic. There's no blood supply. For those of you who remember what ATP is, there's only two produced with glycolysis versus 38-nicarabs cycle. Very inefficient. Let's see. This isn't working. The lens can remain transparent without oxygen in experimental models, but it cannot remain transparent without glucose, even with oxygen present. Glucose is a very important component to the transparency and functionality of the lens in terms of producing the energy that it needs, the ATP that it needs. We're all familiar. I think this is going to go over diabetic. Here we go. What happens with a diabetic? Aldous reductase, a key enzyme in the pathway of processing glucose. There's always a small amount of glucose that goes through this enzyme, but if we get a high amount of sorbitol in the setting of high glucose, glucose is poorly permeable so it will result in the imbibing of water into the lens which can cause the classic myopic shift that you'll see in diabetics we're poorly controlled. Although I've seen several with hyperopic shifts, so it doesn't always end up myopic, but that's sort of the classic. If you see it on the OCAPs, that's probably the answer that would be that question. So again, osmotic pressure drawing that water in is that sorbitol builds up. So there are different protective mechanisms that you can read about more in terms of preventing oxidation and all of these different systems that are used to help with that vitamin C part of that. So vitamin C deficient patient, greater risk of cataract formation. Also the level of oxygen with hyperbaric therapy or vitrectomy, so the mechanism between one of the mechanisms that are thought to be behind the vitrectomy induced cataract is this oxidative stress. We remove the vitreous, causes increased oxygen tension around the lens and increases the rate of that cataract formation, particularly in patients who are over 50. So when you're talking to patients who are considering a vitrectomy, if they're over 50, the risk of cataract formation with a vitrectomy is much higher than some of these under 50. Let's see, lens, physiology, accommodation. So we have several different theories about accommodation. I think most of us are familiar with the Hemholz, which is sort of the classically accepted theory of accommodation. Solar body contracts, decreases the diameter of the rink, ciliary ring, design your attention, decreasing lens increases in circle, curve or shape particularly centrally. That central anterior lens, the greatest change. And it's thought that that change is greater there because of the relatively thinner intercapsules centrally versus equatorially. The loss of accommodation with age. So an adolescent has 12 to 16 doctors, adult age 40. So somebody about my age, 48 diopters. After age 50, it's less than two diopters. And the thought behind this is that the hardening of the lens is the principal cause of presbyopia or the loss of the ability to accommodate just increases in terms of hardening over a thousand fold over a lifetime. Other possible contributing factors include the lens dimension changes relative to the ciliary ring. So as that lens gets larger, you lose a little bit of your functional ability to accommodate as well. Loss of capsillasticity, the geometry of design or attachments, the loss of the equatorial fibers with age. Those are thought to contribute as well. The embryology, 25 days, optic vesicles. This isn't super exciting, but should probably be at least familiar with in terms of embryology. The different ocular structures one may develop and when things can go wrong and how that results in abnormalities. But I won't spend a lot of time. I'll send these slides to anybody that wants them. It's essentially a notes of the BCSE series, this whole lecture. So let's look at some anomalies or abnormalities. Can generally, fakie, a very rare primary and secondary. So either the lens plaque fails to form or is resorbed. Usually you're going to see other ocular abnormalities. A lot of things developing at that moment. Lenticonis and lentoglobus. Lenticonis, of course, is a focal cone-shaped deformation anteriorly or posteriorly, but posterior is more common. It's usually lateral and axial, whereas anterior is often bilateral and associated with Alport syndrome. It's not an uncommon pimp question in the cornea clinic, particularly if they come across it. Let's see. With retinoscopy, you can see this distorted reflex centrally. Reflex might show sort of an oil drop-like appearance because of the difference in the way it's refracting light. And the bulging may progress. You may get an initial myopic shift and eventually maybe a focal opacity in that area as they get older. Metendorf dot. This is something that you will commonly see on a slit lamp exam. It's just a little spot just off-center on the posterior surface of the capsule. It's usually in for a nasal. It's just the remnant of the tunicavascular lensis. Lens coloboma. There are two types, primary and secondary. These are going to be associated. As primary one is associated, just an isolated finding secondary, you're going to see an associated ciliary body's angular defect. They're usually inferior and they're usually associated with the uveal coloboma, so an iris coloboma, maybe a corridor as well. It's important from a surgical planning standpoint to know that you're missing zonules in that area. Usually it's going to be at least a clock hour more than what you think when you're looking at it from an exam standpoint. Peter's anomaly. This is an OCAP test I had, the Pac-6 gene, being knocked out in association with this. It's a spectrum of disorders known as anterior segment dysgenesis. You get the central paracentral corneal opacity or lecoma, and there's thinning war absence of decimates membrane. It's typically thought to be associated with failed separation of the lens vesicle from the surface ectoderm, possible other findings that you might see lens findings. You can see the adhesion between the lens and cornea. You can see anterior cortical or polar cataract changes or a misshapen lens that's displaced anteriorly into the pupil or even into the anterior chamber. Of course, microspherofakia is sort of a classic finding if you don't see some of these other lens findings with Peter's anomaly, that corneal opacity. Microspherofakia is just a small lens. It's a small diameter, it's more spherical in shape. Usually with dilation, you see the full lens equator, and the lens, because of its shape, will result in a myopic area. It's got a steeper curvature. It's most commonly seen in wheel Martiassani syndrome. Of course, we talked about Peter's anomaly. Sometimes it's seen in Alport's Lowe's and Marfan's, congenital rubella. The biggest thing to understand with microspherofakia is spherical lens is there's greater risk of pupil block, angle closure, and myotics will aggravate this because they cause forward lens movement with relaxation with the contraction of the ciliary body. Cycloplegia is sort of a preferred treatment in trying to manage this, which is a little bit unusual. Just because it increases the tensile force on the zonules, of course, an LPI is the ultimate treatment for this form of angle closure. Aniridia, again, another disorder that's associated with Pax gene, allele loss or issues with that specific gene. It's usually a panocular syndrome, but the most striking feature, of course, is the near absence of the iris. Associated findings, corneal panacea and epitheliopathy. You will see an association with aniridia with, I believe, an ethereal dysfunction as well. Acoma can be associated with that due to abnormality in terms of the developmental anomalies associated with the trabecular mesh work structures. Sometimes we'll see optic nerve hypoplasia and nystagmus due to poor visual potential. It's almost always bilateral. You can see two-third cases, one-third sporadic. Sporadic cases are often seen with a wider complex. You can't see cataract changes. You see focal polar opacities. And cataracts are very common within the first two decades of life. Congenital cataracts, by definition, is present at birth within the first year of life. It will occur in approximately one in 2,000 live births. You can kind of use this basic third of them are syndrome-related of them. Third of them are isolated, inherited. And third of them are unknown cause if we do a workup. Table 3-1 in the BCSE series has a list of different potential causes. A lamellar or zonular cataract is the most common type of congenital opacity. A lot of these are bilateral, symmetric with that. So polar cataract is just a focal opacity of the subcapsular cortex or capsule anteriorly or posteriorly. Anterior is typically small, bilateral, not typically visually significant. And usually it doesn't require surgery, but sometimes it can cost anisomatropia. So you've got to be aware of that, looking for that. Because of course that can be associated with the development of amblyopia. Posture is more commonly visually significant because it's closer to the nodal point of the eye. So it's an optics concept. We all, I think, are familiar with the association with capsular fragility. So greater risk of posture capsular either at defect or what is thought to be just fragility where it's a greater risk of posture capsule break with cataract surgery in the setting of a true posterior polar cataract. A few other different types. Cerulean, this is one that I'll see every so often a couple of times a year. It's sort of these small bluish opacities in the lens cortex. They're not progressive, not typically visually symptomatic, but pretty impressive in terms of the exam features. Let's see. So ectopia lentus, let's talk about this here. So this can be a congenital issue, a developmental issue. It can be acquired, of course, from trauma. Subluxated means there's a partially displacement, but you can still see the lens within the pupil. Luxated or dislocated, it's completely displaced from the pupil, which implies a loss of all zonular support. Obviously symptoms will include decreased vision. We'll see marked astigmatism due to the displacement of the lens, monocular deplopia, iridinesis. Complications include cataract, a displacement of the lens into the AC or vitreous. In the AC, of course, we can get pupil block and acute angle closure. So acquired, obviously, is we talk about trauma. These are associated with ectopia lentus. It's going to be associated with Marfan syndrome, homocystinuria, and iridia, like we talked about. There's Danlos, hyperlysinemia, sulfide oxidase deficiency. And it can be inherited as an isolated anomaly and an autosomal dominant inheritance pattern. But important to know some of these associations are more commonly Marfan's. Just be aware of the different associations with these systemic syndromes and where the lens is more likely to be displaced. With Marfan's, so Marfan's autosomal dominant inheritance, about 15% of patients with Marfan's will have no family history. Of course, the mutation of the fibrillin gene, these patients, we know they're tall. They have arachnidactyly, chest wall deformities. Aortic roots dilation and malformations are common. Mitral valve prolapse also a big issue. These patients are at increased risk for sudden cardiac events. Let's see. About 50 to 80% of patients with Marfan syndrome will show ectopia lentus, usually symmetric or superior in temporal displace on the lens. Designals will remain intact, but are stretched elongated. When you're looking at a patient with lens subluxation, is there any way to tell whether the zonules are stronger in one area versus another? Anybody know what the lens would look like in that scenario? So let's say the lens is displaced in one direction and it's misshapen, where it's not completely spherical, one area looks like a little bit flatter. If you see that, that would suggest the zonules on that side are a little bit stronger. That's what's creating that misshapen, tensile strength in the one side versus the other, whereas if the lens is completely spherical, even though it's displaced, that would suggest the zonules are weak throughout. That's just a physical finding that you might see that would suggest the zonules may be a little bit stronger, at least in some areas, with one scenario versus another. So just something to be aware of. With Marfan's, has anybody seen a Marfan's patient that didn't have ectopia lentus? I've seen one. We don't see a lot of Marfan's patients, but we see enough of them that we see this not infrequently, particularly if you work with Alan Crandley. You'll see those. These are referred to him directly. Of course, other eye findings, they're myopic. There's increased risk of retinal detachment. Minor increase in the risk of glaucoma, amblyopia is of concern because of the high ametropia that they often have. They will often have weak or absent accommodation at younger ages, so if they're complaining about near vision symptoms, then don't hesitate to put them in a bifocal. Lensactomy is associated with increased risk of vitreous loss and retinal detachment, so always there's this balance of deciding when to do surgery, in terms of the impact on vision and the risks associated with surgery. Homocystinary, we won't worry about that. Prolysonymia. So genetic contribution to age-related cataracts. So we look at identical and fraternal twin studies. This suggests there's at least a component of age-related or heritable component of age-related cataract. The BCSE series suggests that 50% of cortical cataract risk is genetic or heritable. You can see this mutation is gene E-P-H-A-2. You familiar with that, Nico? Have you ever heard of that one? No? Okay. Neither have I. Other than when I would type this. 35% of nuclear cataract is thought to be heritable as well. Which suggests that study of genetic links and underlying biological pathways may be important to assisting us in understanding potential targets for therapy. This is not good for business, so I don't want any of you to spend any time looking for this. Let's see, ectopia lentis at pupilae. This is an autosomal recessive. We talked about isolated ectopia lentis being an autosomal dominantly inherited condition. If you see ectopia lentis with pupil abnormalities, this is typically autosomal recessive. The lens and pupil are displaced in opposite directions. Irregular and slit-shaped. This is typically bilateral, but it can be asymmetric. Pupil will be poorly dilated. Associated ocular anomalies, you can see again, sometimes associated with axiomyopia, retinal detachment, of course, in association with that, enlarged corneal diameter, cataract, and trans-illumination defects of the iris. Persistent fetal vasculature P-F-V or persistent hyperplastic primary vitreous P-H-P-V is congenital and non-hereditary. It's usually unilateral. We'll see this white fibrous retrolental tissue. Often with posterior cortical apacitation, cataract progression is very common in these patients. And they, of course, have associated ocular anomalies. Elongated ciliary processes, prominent radial iris vessels, and persistent hyalurid artery. They usually have a fairly poor visual prognosis, though. The extent of the changes can be quite varied, and that will have an impact on their visual potential. How you assess that. So let's talk, let's see if we have a few minutes left. Age-related cataract changes. With age, of course, the lens increases mass thickness. There's a decrease in accommodative power. With new layers of cortex, of course, the central lens is compressed and hardens. We get nuclear sclerosis. Chemical changes that we've talked about before and issues with processing of these crystallines will result in these high molecular mass protein aggregates. They can become large enough to cause little abrupt changes in the index of refraction and result in focal light scattering, reduced transparency. It's always interesting to me how different cataract, the appearance may not look all that much different, but the impact on vision for some patients is much greater than others, and probably a lot of that has to do with these focal areas, these sudden changes or abrupt changes in index of refraction, which results in greater amounts of light scattering. Sometimes it'll be impressive when you look at a cataract and think there's just nothing impressive about this. You go through the entire workup looking for something else to cause the vision changes and it all ends up coming back to the very amount of cataract that you're seeing. So again, this can have a significant role in visual function. Of course, we are all familiar with the chemical modifications of nuclear proteins, what it looks like on exam, yellowish going to brown eventually, decrease in potassium and glutathione, increase in sodium and calcium in terms of cell cytoplasm. I saw that on an OCAPS many years ago, that question. So nuclear cataracts, you know, there's some level of sclerosis, which is normal after the age of 50. It's a central opacity. We evaluated the slit lamp. You can sometimes see it with the red reflex when you're looking at the direct ophthalmoscope. Usually it's very slowly progressive, typically bilateral, though it can be asymmetric. It's greatest impact when you're looking at nuclear cataract's distance vision. Usually they see fairly well up close, myopic shift, the second sight. There's a reduced color discrimination. I think we're all familiar talking to post op patients, talking about how their color perception has improved significantly. They didn't realize the impact. This is particularly prominent to the blue end of the spectrum, shorter wavelengths. Histologically, it's not much different than a clear lens. Not sure that's really important, but it's there. So cortical cataracts, you get local disruption of cell structure, of mature lens fibers. Usually this is an issue of the membrane integrity being compromised. So you lose the essential metabolites. We get oxidation, precipitation. It's usually bilateral, but it's often asymmetric, as we know. The effect on vision depends on the location. So they're just peripheral cortical spokes. You're not seeing a lot of impact on vision. But of course glare is a common symptom from focal light sources when we see significant cortical changes. Progression with ease is a little less predictable. Some are very stable, as we know, when we see them year over year, just the same minor cortical changes. In other cases, they can be fairly rapidly progressive. Your first findings, vacuoles in the lens, water clefs, and then of course, spokes, these wedge-shaped opacities. We know with complete cortical opacification, it's mature. The cortex can take up water, causing swellings of intimescence. Younger patients with white cataracts, they're intimesant until proven otherwise. Very old patients or older patients with white cataracts, that's usually going to be a rock and not necessarily intimesant. Just sort of a general rule of thumb on those. When the degenerated cortex leaks through the capsule, it'll wrinkle and shrink. We call that hyper-mature. With further liquefaction of cortex, it allows the nucleus to float freely within the capsule. We call that a morgagnian cataract. That's posterior subcapsular cataracts. Often younger age of it onset. Most commonly, it's posterior and axial in location. Of course, glare symptoms, poor vision with bright lights or bright lit backgrounds. Light will induce pupil constriction, which results in greater potential impact, particularly if it's centrally located. And near vision is often more affected, of course, with accommodation, the pupil constricts as well. Usually, the times of patients are going to complain about that most commonly. It causes, of course, sometimes it's age, trauma, steroid use, inflammation, ionizing radiation, alcoholism, diabetes. The histology, we get these posterior migrations of lens epithelial cells from the lens equator, followed by aberrant enlargement swollen cells called Wettler bladder cells. PSC and PCO have a lot of overlap in terms of their pathology, how they develop. Let's see, we talked about some drug induced. We talked about steroids and PSC association. There are a few other drugs that can cause lens changes, phenothiazines, myotics. Let's see, amiodarone is really visually significant. Statins, studies in dogs, showed cataracts with high doses. Human studies have shown some modest reduction in cataract formation. Talked about trauma, radiation. Let's see how many more slides there are. I think we talked a little bit about diabetic cataract before. So effects of nutrition, alcohol, and smogang, this is more important to adjust. Lower socioeconomic status, education level, poor overall nutrition is associated with age-related cataracts. We talked about vitamin C, some of the antioxidants. Though there are conflicting results with those studies, the ARED study showed no difference in terms of vitamin supplementation. Let's see, Lutine and Ziazanthine are the only carotenoids found in the human lens. Interesting trivia question. I think that's about all I can think of with that. So smoking, tobacco products are excessive. Alcohol consumption is associated with cataract and of course age-related macular degeneration. So these are important things. Smoking is an independent risk factor for the development of cataract. We all know that uveitis can be associated classically subcapsular cataracts, corticosteroids. Betrectomy, we talked about that and the mechanism behind it. Hyperbaric oxygen. Pseudo-exfoliation is probably the last thing we're going to touch on. So this is a fibro-legranular material deposited in the irons that are organs. It's a basement membrane-like material. When we look in the eyes, it's deposited on the lens cornea, trabecular meshwork, iris-related process, anterior-hydrolyphasins on your fibers. You'll see atrophy of the iris at the pupil margin, pigment deposition on the interior iris, they often poorly dilate. Increased pigmentation you'll see in the trabecular meshwork on gonioscopy. Capsule fragility is a concern. Zinular weakness is a concern. Both with cataract surgery and, of course, long-term possible spontaneous lens subluxation with a pseudophagic state, open-angle glaucoma association with that. It can be unilateral or bilateral on exam or presentation, though it's always presumed to be bilateral and it's more apparent, of course, with increasing age. So it's an important thing to look for when you're signing up cataract patients. We know we do that consistently at the VA just to warn the surgeons about the potential increased risk of these different issues, poor pupil dilation, zinular weakness. Does anybody have any questions?