Plasmapheresis in ophthalmology

PLASMAPHERESIS IN OPHTHALMOLOGY 

V.A.Voinov

Pavlov First St. Petersburg State Medical University, Saint-Petersburg, Russia.
.

Summary 

Many eye diseases are autoimmune nature and are accompanied by the accumulation of autoantibodies as well as other pathological metabolites, the large size of the molecules which do not allow them to remove them through kidneys and in violation of the processes of their degradation. Removing them is possible only with the liquid portion of blood - plasma during plasmapheresis, which allows to treat such diseases more efficiently.

Keywords: eye diseases, autoantibodies, plasmapheresis.

Plasmapheresis finds its application in a number of autoimmune diseases, including in ophthalmology.

Diabetic retinopathy, which leads to irreversible vision loss is a result of vascular lesions of the retina secondary toxic metabolites arising in the long course of diabetes. The fact that the diet, drug therapy, insulin allow to keep blood sugar levels, but did not prevent it from vavering, which leads to a variety of secondary metabolic disorders mainly vascular. In this case, one of the causes of angiopathy in diabetes is to increase platelet aggregation, which depends not only on the magnitude of the concentration of sugar in the blood, but from some other pathological products affecting platelet membrane [Mazzanti L. et al., 1997].

In the pathogenesis of diabetic retinopathy play a role not only to the accumulation of endotoxic metabolic products with signs of chronic DIC, but also immunological disorder – low T-cell immunity with increased the circulating immune complexes (CIC) of 81% of patients [Balashova L.M. et al. 1999].  

In addition, there is described also idiopathic autoimmune retinopathy, when the progressive degeneration of the retina occurred in response to anti-retinal autoantibodies are detected in the serum of these patients [Mizener JB et al., 1997]. It may result in vessels and in antiphospholipid syndrome also [Tsironi E. et al., 2009; Utz V.M., Tang J., 2011].

The main treatments for proliferative diabetic retinopathy are panretinal laser coagulation of the retina and transciliary vitrectomy. However, the incidence of adverse outcomes in this case remains fairly high [Sdobnikov S.V., Stolyarenko G.E., 1999].

L.M. Balashova et al. (1999) using intravascular laser irradiation of blood with Inhaled heparin, made ​​to reduce swelling of the macular area (80% of cases), partial resorption of hemorrhages (58%), reducing the caliber veins (43%), improving visual acuity 0.03-0.3, increasing the field of view. Of course, it is necessary to use also various methods of drug therapy.

However, an even greater effect gives therapeutic apheresis removing these pathological products, which makes it possible to stop or mitigate these vascular disorders. There is proved the effectiveness of plasmapheresis also at retinopathy accompanying hyperviscous syndrome (Waldenstrom's macroglobulinemia). This not only reduces the level of IgM by 46.5% and blood viscosity by 44.7%, but the diameter of the varices by 15.3% with an increase in venous blood flow to 55,2% [Menke M.N. et al., 2008, 2009; Chanana B. et al., 2009]. The plasma exchange was applied and at a lupus retinal vasculopathy [Papadaki T.G. et al., 2006].

Circulatory disturbances in the optic disc are the leading cause of visual loss in people over 50 years old. Anterior ischemic optic neuropathy is the result of reduction of perfusion in the posterior short ciliary arteries in hypercholesterolemia, high blood viscosity, hyperglycemia, regional vascular endothelial disorders, arterial hypertension. Cascade plasmapheresis (600 ml concentrate plasma) has enhanced visual acuity from 0.10 ± 0.03 to 0.35 ± 0.05, reduce central scotoma, enlarge the boundaries of peripheral visual field on a background of a two-fold reduction in the level of cholesterol, triglycerides, plasma fibrinogen [Filonenko I.V., Konovalov G.A. , 2003]. Similar results using cascade plasmapheresis achieved also M. Bláha et al. (2009).

As is known, formation of antibodies to self antigens is blocked as long as these antigens as a result of some pathologic processes (inflammatory injury) did not alter its structure so that it no longer perceived "their own" and against which triggers the formation of antibodies. Perhaps that is why, after all sorts of diseases choroidal lesion often develops and the other eye – sympathetic ophthalmia, as a result of an autoimmune process, and only the removal out of the body of these autoantibodies formed prevents loss of the healthy eye.

In addition, it is the described immunization to own lens antigens damaged during cataract operations, followed by immune inflammation of the eye –  foko-anaphylactic endophthalmitis.  

Neuromyelitis optic nerve is a form of demyelinating diseases of the nervous system (Devic’s disease). It often combined with the spinal cord damage. Therapeutic measures include corticosteroids and plasmapheresis [Argyriu A.A., Markis N., 2008].

Autoimmune processes also determine the course of uveitis, which results in 30% of patients with disabilities, including blindness (10%) [Zaitsev, N.S., Katznelson L.A., 1984]. Uveitis accompany many system autoimmune diseases – lupus erythematosus, sarcoid, rheumatoid arthritis, polyarteritis nidisa, diseases of Buerger and Kawasaki, system vasculitides andalso such systemic pathology as Behcet's disease, indicating that they have overall mechanisms of their autoimmune pathogenesis [Numazaki K. et al., 1997; van Daele P.L.A. et al., 2009; Levitt A.E. et al., 2015]. Immunological studies indicate an increase in the blood levels of active T-cells, B-cells and the CIC, increased secretory IgG in the tear fluid. In the latter it can also be found antibodies to eye tissues – to the retina, the lens and the cornea, even [Tretiak E.B. et al., 2006].

Developing cellular infiltration of the vitreous to form in it cyclic membranes complicated with cataract, exudative hemorrhagic form of inflammation of the choroid and retina [Chentsova O.B., 1999]. Experiments on animals have also shown the important role of nitric oxide (NO) in the pathogenesis of autoimmune uveoretinitis [Hoey S. et al., 1997]. Chorioretinopathy seems chronic bilateral posterior uveitis, an autoimmune form of nature. Without treatment it leads to photophobia, night blindness, visual field loss and blindness. In some cases, patients with uveitis detect antibody class IgG, IgA and IgM antibodies to Chlamydia pneumoniae.

In the treatment of acute postoperative uveitis courses of plasmapheresis can reduce the incidence of inflammatory complications, reduce the time and improve the overall results of treatment [Fomin A.M. et al. 2006, 2012].

 The most commonly used long steroid therapy and cyclosporine, which are side effects of cataracts, osteoporosis, diabetes, and hypertension [Karmochkine M., Kazatchkine M.D., 1998]. Usual immunosuppressive therapy and cytotoxic drugs do not prevent recurrent exacerbations and an introduction to the range of therapeutic interventions plasmapheresis provides more stable results [Malecaze F. et al., 1989; Chentsova O.B. et al. 1994, 2006; Frolov A.B. et al., 2009; Onishchenko A.L. et al., 2011]. Plasmapheresis or plasma exchange with replacement cryo sorbed autoplasma to 50% CPV contribute to more rapid relief of the inflammatory process, the transition to a state of remission, disappearance of adhesions, even without local proteolytic therapy [Danilichev V.F. et al., 2013].

Such treatment is indicated for the prevention of recurrence of uveitis [Sokolov A.A. et al. 2003]. Plasma exchange with extracorporeal blood laser irradiation are indicated in autoimmune diseases of the eye, even in children [Grechanyj M.P. et al., 2003].

Graves' ophthalmopathy is organ specific autoimmune disease in which there is infiltration of mononuclear cells of tissues of the orbit with the local release of cytokines, indicating the role of activated T-lymphocytes in its pathogenesis. During this active inflammatory phase in the retrobulbar tissue occur lymphocytic infiltration and interstitial edema jet. Immunosuppression depresses this immune inflammation. There is the efficiency of the application also massive doses of immunoglobulins to 2 g intravenously daily for 5 days [Kahaly G. et al., 1996]. Close to such an ophthalmopathy and proptosis, there are often accompanied by lesions of the thyroid gland, which is also effective when plasmapheresis[Bartalena L. et al., 1997; Katoh N. et al., 2010].

Resistant viral conjunctivitis is often the result of the weakened immune defense mechanisms. Detection of antibodies to Chlamidia pneumoniae in some of these patients points to a possible link also. Since immunosuppression usually occur on the background of some biochemical changes, the reorganization of the internal environment with plasmapheresis and laser immunostimulation, restoring the broken links of immunity, promote healing these diseases also.

There is the development of keratoconjunctivitis allergic nature perhaps, because in such cases, they are often combined with atopic dermatitis. They are characterized by the epithelium micro erosions, persistent epithelial defects, severe corneal vascularization and haze [Messmer E.M., 2005; Maichuk Y.F., 2006]. There is perhaps the development also of autoimmune "dry" keratoconjunctivitis (xerophthalmia) with Sjögren's syndrome [Cejková J. et al., 2009]. The plasma exchange helped and with such casesalso [Mach R. etv al., 1992].

Severe optic neuritis, in some cases of poisoning with some toxic substances (eg, methanol), and only emergency and massive therapeutic apheresis can prevent irreversible vision loss in these cases.

Ophthalmoplegiamay develop as a result of an autoimmune destruction of the eye muscles. Thus, IgG anti-GQ1b antibodies are closely associated with acute paresis of the external ocular muscles (manifested of diplopia) after infection or immunization. But it could be an isolated paresis internal eye muscles – this is an internal ophthalmoplegia, manifested mydriasis and photophobia. These reactions are common in patients with Fisher or Guillain-Barre syndromes [Suzuki T. et al., 1998; Yuki N. et al., 1998] and plasmapheresis helps in such accidents [Ejma M. et al., 2015].

Lattice corneal dystrophy type IIIA accompanied by recurrent corneal erosions. This disease is autosomal  form of the genetic pathology, in which the gene product big-h3 is a secretory protein (68kD keratoepithelin), detectable in the cornea. In this case, there appear autoantibodies to big-h3, which leads to the degeneration of the cornea and its deposition in its stroma  subepithelial and intrastromal of amyloid [Kawasaki S. et al., 1999]. In these cases, removal of autoantibodies is also useful [Sobue G., 1999.

M.L.Korolev et al. (2000) consider indicated plasmapheresis in patients with uveitis, diabetic retinopathy, optic neuritis and vascular diseases of the eye (thrombosis, atherosclerosis). The use of plasmapheresis has a positive effect and in elderly patients with pathology of the vision [Gavrilov A.O. et al., 2004; Pulido J.S. et al., 2005].

Senile macular degeneration develops due to deposition of protein structures between the chorion capillaris and the retinal pigment epithelium, leading to the development of the central scotoma with a significant loss of vision. This is accompanied by disorders of microcirculation and in combination with hypercholesterolemia and hyperfibrinogenemia. Microcirculatory disorders violate nutrition and oxygen delivery to the cells of the retinal pigment epithelium. Prospective multicenter randomized trials have shown the effectiveness of courses of plasmapheresis with subsequent cascade filtration up to 8 treatments for 10 weeks [Pulido J.S., 2002]. The positive effect was maintained even in 3 and 12 months [Pulido J. et al., 2005, 2006; Yeh J.H. et al., 2008; Klingel R. et al., 2010; Rencova E. et al., 2011]. M.J.Koss et al. (2009) believed that there are no other therapeutic alternatives in this pathology except cascade plasmapheresis. According to the recommendations of American society for apheresis (ASFA), reo apheresis is the method of choice in the treatment of this disease [Schwartz J. et al., 2013].

With plasmapheresis achieved a beneficial effect also for a post-traumatic ophthalmopathy. At the same time, along with more rapid relief of inflammatory processes in the eye there were resolved opacities in the vitreous and hemorrhage in the fundus, central visual acuity increased by 20-30%, for 4-5 days reduced the time of treatment of such patients [Riabtseva A.A. et al. 2004].

Bilateral diffuse melanocytic proliferation of the choroid is a type of paraneoplastic syndrome. With plasmapheresis prevents thickening of the choroid with the improvement of [Mets RB et al., 2011].

Thus, given the large size of autoantibodies as well as other pathological metabolites that kidneys are not taken and they tend to accumulate, just using plasmapheresis possible their effective removal [Voinov V.A., 2010]. Usually requires a course of plasmapheresis, consisting of four sessions as the plasma volume in about 1% of body weight every time that the whole of the course is 1-1.5 CPV. Simplicity and safety of plasmapheresis on Russian devices Hemofenix allows such treatment in almost any medical facility until their municipal managers. Therefore, plasmapheresis, and should take its rightful place in the treatment of many eye diseases.

 

 

 

References

 

Argyriu A.A., Markis N. Neuromyelitis optica: a distinct demyelinating disease of the central nervous system // Acta Neurol. Scand. 2008. – Vol. 118, № 4. – P. 209-217.

Balashova L.M., Teplinskaya L.E., Zaitsev N.S. et al. [Use of inhaled heparin in combination with intravenous laser irradiation of blood in patients with diabetic retinopathy] // Vestn. oftalmol. (Rus.) – 1999, № 1. –  P. 16-18.

Bláha M., Rencová E., Bláha V et al.The importance of rheological parameters in therapy of microcirculatory disorders // Clin. Hemorheol. Microcirc. – 2009. – Vol. 42, № 1. – P. 37-46.

Cejková J., Ardan T., Cejka C. et al.  Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness // Histol. Histopathol. – 2009. – Vol. 24, № 10. – Р. 1357-1365.

Chanana B., Gupta N., Azad R.V. Case report: bilateral simultaneous central retinal vein occlusion in Waldenström’s macroglobulinemia // Optometry. – 2009. – Vol. 80, № 7. – P. 350-353.

Chentsova O.B., Shabalin V.N., Grechanyj M.P. [Combined use of plasma exchange with laser irradiation of blood in complex treatmentof endogenous and traumatic uveitis (Guidelines)] (Rus). // Moscow. – 1994. – 18 p.

Chentsova O.B. [Clinical and immunological criteria for prognosis of uveitis] // Vestn. Ophtalmol. (Rus.). – 1999, № 2. – P. 23-25​​.

Chentsova O.B., Grechanyj M.P., Kildyushevskii A.V., Tretiak E.B. [Prospects for the use of extracorporeal blood correction in the treatment of autoimmune eye diseases]// Vestn. Ophthalmol. (Rus.). – 2006, № 3. –  P. 115-117.

Danilichev V.F., Chshieva M.R., Sokolov A.A. [Possibility of therapeutic apheresis in the treatment of patients with chronic recurrent uveitis] // Efferent therapy. (Rus.). –  2013. –  Vol. 19, № 1. – P. 64-65.

Filonenko I.V., Konovalov G.A. [Reo-pheresis in treatment of circulatory disorders in the optic nerve head] // Proc. XI Confer. Moscow hemapheresis society. – Moscow –  2003. –- P. 63-64. (Rus.).

Fomin A.M., Riabtseva A.A., Aladdin A. [Efficacy of plasmapheresis in acute postoperative uveitis] // Proc. XIV Confer. Moscow hemapheresis society. – Moscow.  – 2006. – P. 50. (Rus.).

Fomin A.M., Riabtseva A.A. [Therapeutic plasmapheresis in acute postoperative uveitis / Proc. XX Confer. Moscow hemapheresis society. – Dubna. – 2012. – P. 135-136. (Rus.).

Frolov A.B., Grechanyj M.P., Chentsova O.В. [The use of extracorporeal blood correction on the basis of plasmapheresis in the treatment of endogenous uveitis and autoimmune eye diseases] // Vestn. Oftalmol. (Rus.). – 2009. – Vol. 125, № 5. –  P. 57-60.

Gavrilov A.O., Chumaeva E.A., Krutii N.A. et al. [Changes hemo-agregatogram patients with pathology of organ vision at various methods of therapy] // Proc. XII confer. Moscow. hemapheresis society. - Moscow, 2004 - P. 13. (Rus.).

Grechanyj M.P., Chentsova O.B., Kildyushevskii A.V. [Extracorporeal hemocorrection in the treatment of autoimmune diseases of the eye in children] // Russian Medical Journal. – 2003 – Vol.4, № 4. – P. 14-16. (Rus.).

Hoey S., Grabowski P.S., Ralston S.H.et al. Nitric oxide accelerates the onset and increases the severity of experimental autoimmune uveoretinitis through an IFN-g-dependent mechanism // J. Immunol. - 1997. - Vol. 159, № 10. - P. - 5132-5142.

Kahaly G., Pitz S., Műller-Forell W., Hommel G. et al. Randomized trial of intravenous immunoglobulins versus prednisolone in Grave’ ophthalmopathy  // Clin. Exp. Immunol. - 1996. - Vol. 106, № 2. - P. 197-202.

Karmochkine M., Kazatchkine M.D. Intravenous immune globulin in autoimmune uveitis // Ann. Intern. Med. – 1998. – Vol. 129, № 12. – P. 1078-1079.

Kawasaki S., Nishida K., Quantock A.J. et al. Amyloid and pro 501thr-mutated  big-h3 gene product colocakize in lattice corneal dystrophy type IIIA // Am. J. Ophthalmol. - 1999. - Vol. 127, № 4. - P. 456-458.

Klingel R., Fassbender C., Heibges A. et al. RheoNet registry analysis of rheopheresis for microcirculatory disorders with a focus on age-related macular degeneration // Ther. Apher. Dial. – 2010. – Vol. 14, № 3. – P. 276-286.

Korolev M.L., Osadchikh V.G., Ikonnikova T.B. et al. [The need for extracorporeal blood surgery methods for the ophthalmology department of the city hospital plasmapheresis] // Proc. VIII Confer. Moscow hemapheresis society. – Moscow. –  2000 –  P. 132. (Rus).

Koss M.J., Kurz P., Tsobanelis T. et al. Prospective, randomized, controlled clinical study evaluating the efficacy of Rheopheresis for dry age-related macular degeneration. Dry AMD treatment with Rheopheresis Trial-ART // Grafes Arch. Clin. Exp. Ophthalmol. – 2009. – Vol. 247, № 10. – P. 1297-1306.

MaichukY.F.,PozdnjakovV.I.,LortkipanidzeM.M.,PozdnjakovaV.V. [Eyelesionsinpatientswithatopicdermatitis] // AllergologyandImmunology (Rus.). – 2006 – Vol. 7, № 3. – Р. 424.

Mazzanti L., Robini R.A., Fumelli P. et al. Altered platelet membrane dynamic properties in type 1 diabetes // Diabetes. - 1997. - Vol. 46, № 12. - P. 2069-2074.

Menke M.N., Feke G.T., McMeel J.W., Treon S.P. Effect of plasmapheresis on hyperviscosity-related retinopaty and retinal hemodinamics in patients with Waldenstrom”s macroglobulinemia // Invest. Ophthalmol. Vis. Sci. – 2008. – Vol. 49, № 3. – P. 1157-1160.

Menke M.N., Feke G.T., McMeel J.W., Treon S.P. Ophthalmologic techniques to assess the severity of hyperviscosity syndrome and the effect of plasmapheresis in patients with Waldenström’s macroglobulinemia // Clin. Lymphoma Myeloma. – 2009. – Vol. 9, № 1. – P. 100-103. 

Mizener J.B., Kimura A.E., Adamus G. et al. Autoimmune retinoparty in the absence of cancer // Am. J. Ophthalmol. - 1997. - Vol. 123, № 5. - P. 607-618.

Numazaki K., Chiba S., Aoki K. et al. Detection of serum antibodies to Chlamydia pneumoniae in patients with endogenous uveitis and acute conjunctivitis // Clin. Infect. Dis. - 1997. - Vol. 25, № 4. - P. 928-929.

Mets R.B., Golchet P., Jampol L.M. Bilateral diffuse uveal melanocytic proliferation with a positive ophthalmoscopic and visual response to plasmapheresis // Arch. Ophthalmol. – 2011. – Vol. 129, № 9. – P. 1235-1238.

Pulido J.S. Multicenter prospective, randomized, double-masked, placebo-controlled study of Rheopheresis to treat nonexudative age-related macular degeneration: interim analysis // Trans. Am. Ophthalmol. Soc. – 2002. – Vol. 100, № 1. – P. 85-106.

Pulido J., Sanders D., Winters D., Klingel R.  Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration // J. Clin. Apher. – 2005. – Vol. 20. – P.185-194.

Pulido J.S., Sanders D., Klingel R. Rheopheresis for age-related macular degeneration: clinical results and putative mechanism of action // Can. J. Ophthalmol. – 2005. – Vol. 40, № 3. – P. 332-340.

Pulido J.S., Winters J.L., Boyer D. Preliminary analysis of the final multicenter investigation of rheopheresis for age related macular degeneration (AMD) trial (MIRA-1) results // Trans. Am. Ophthalmol. Soc. – 2006. – Vol. 104. – P. 221-231.

Rencova E., Blaha M., Studicka J. et al. Haemorheopheresis could block the  progression of the dry form of age-related macular degeneration with soft drusen to the neovascular form // Acta Ophthalmologica. – 2011. – Vol. 89. – P. 463-471.

Riabtseva A.A., Fomin A.M., Savchuk G.V., Kryuchkov O.S. [Plasmapheresis in trauma of the vision] // Proc. XII confer. Moscow hemapheresis society. – Moscow. –  2004 - P. 51. (Rus).

Sdobnikov S.V., Stolyarenko G.E. [The role of the back of the hyaloid membrane in the pathogenesis and trans-ciliary surgery of proliferative diabetic retinopathy] // Vestn. oftalmol. (Rus.). – 1999, № 1. – P. 11-13.

Sokolov A.A., Danilichev V.F., Belskyh A.N., Knorring G.Y. [Place of extracorporeal immunomodulation and systemic enzyme therapy in complex treatment of organ-specific autoimmune diseases of the eye] // Efferent therapy. (Rus.). – 2003. –  Vol. 9, № 1. – P. 119-120.

Suzuki T., Chiba A., Kusunoki S. et al. Anti-CQ1b ganglioside antibody and ophthalmoplegia of undeterminal cause // Brit. J. Ophthalmol. – 1998. – Vol. 82, № 8. – P. 916-918.

Schwartz J., Winters J.L., Padmanabhan A. et al. Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the writing committee of the American Society for Apheresis: the Sixth Special Issue // J. Clin. Apher. – 2013. – Vol. 28. – P. 145-284.

Tretiak E.B., Trubilin V.N. Syroedova O.N., Suchkov S.V./ [Specific and non-specific autoantibodies in the pathogenesis of localized forms of autoimmune inflammation] // Allergology and Immunology (Rus.). – 2006 – Vol. 7, № 3. - P. 425-426.

Tsironi E., Gatselis N., Kotoula M.G. et al. Ocular disorders as prevailing manifestations of antiphospholipid syndrome: a case series // Cases J. – 2009. – Vol. 2. – P. 159.

Utz V.M., Tang J. Ocular manifestations of the antiphospholipid syndrome // Br. J. Ophthalmol. – 2011. – Vol. 95, № 4. – P. 454-459.

Van Daele P.L.A., Kappen J.H., van Hagen P.M., van Laar J.A.M. Managing Behçet disease: An update on current and emerging treatment options // Ther. Clin. Risk. Manag. – 2009, № 5. – P.385-390.

Voinov V.A. [Efferent therapy. Membrane plasmapheresis] / Moscow, 2010. – 400 p. (Rus.).

Yeh J.H., Cheng C.K., Chiu H.C. A case report of doble-filtration plasmapheresis for the treatment of age-related macular degeneration // Ther. Apher. Dial. – 2008. – Vol. 12, № 6. – P. 500-504.

Yuki N., Koda M., Hirata K. Isolated internal ophthalmoplegia associated with immunoglobulin G anti-GQ1b antibody // Neurology. – 1998. – Vol. 51, № 5. – P. 1515-1516.

Zaitsev N.S., Katznelson L.A. [Uveitis]. / Moscow. – 1984 – 120 p. (Rus.).

Back
You can leave a message using the form below:
Thank you.

We will contact you soon!
Leave request for training by completing the form below:
Thank you.

We will contact you soon!